"This shows we can really target Down syndrome pharmacologically," said Dierrsen.
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And unlike marijuana, hemp's uses go beyond its pharmacologically active compounds.
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So if you could block that receptor [in humans], pharmacologically, you could induce infertility.
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"We compared a pharmacologically-induced altered state of consciousness with our computer-generated simulation," he says.
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That brought it a bit closer to the 500-gram threshold for powder cocaine, which is pharmacologically similar to crack.
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Still, any time we tinker with the human brain — either pharmacologically, electrically, or physically — we obviously need to be careful.
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" The claims echo former NJOY CEO Craig Weiss, who said in a 2013 CNBC appearance: "Pharmacologically, it's very similar to caffeine.
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"Pharmacologically, there is the possibility that MDMA causes changes in the brain that are just not the same [afterward]," says Sessa.
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" The research is still in the exploratory mode, Alves noted, "but we have demonstrated that you can pharmacologically manipulate aspects of disease.
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In general, he told them, more than one-third of patients would get better when given a treatment that was, pharmacologically speaking, inert.
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Treating A.D.H.D. pharmacologically or behaviorally may essentially be an exercise in social conformity, not a medical or psychological intervention to correct a genetic or neurological abnormality.
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At one point, the federal sentence for crack possession was 100 times harsher than it was for powder cocaine, even though the drugs are pharmacologically similar.
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On Tuesday, Biogen said a new analysis of a larger dataset showed that the drug was "pharmacologically and clinically active" in trial participants who have Alzheimer's.
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But on Tuesday, Biogen said a new analysis of a larger dataset showed that the drug was "pharmacologically and clinically active" in trial participants who have Alzheimer's.
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With that, Getty buys Paul a plane ticket back to Rome, sans check, just before he welcomes his mistress into his study for some pharmacologically enhanced sex.
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"There is a real need for cannabis varieties for potential medical use that produce modulated THC concentrations and varying concentrations of other pharmacologically active substances," the patent says.
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"It's actually probably not that dangerous if you think about it pharmacologically in folks that are adults over 25, but among youth, it actually is hazardous," Rosenthal said.
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They found similar changes in signal diversity even though the drugs are very different, pharmacologically, and noted that people who reported more intense experiences had more brain signal changes.
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Cuomo's initiative providing much-needed hand sanitizer, though perhaps less pharmacologically sexy than Civica Rx's antibiotics and blood thinners, serves a similarly laudable public health goal in an innovative fashion.
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It grows in Western equatorial Africa, from Cameroon to Angola, and belongs to the family Apocynaceae, which Alexander Shulgin called the richest single source of pharmacologically active compounds in the plant kingdom.
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The connection was part of the rationale for making it 100 times easier to get a mandatory minimum sentence for crack cocaine over powder cocaine, even though the two drugs are pharmacologically identical.
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As with his running, he pushed so hard with his coaching methods that he crossed a line, veering from the questionable to the pharmacologically impermissible, according to the United States Anti-Doping Agency.
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Every venomous animal has a unique chemical cocktail made from dozens to thousands of compounds, many of which have pharmacologically-useful effects on our bodies, such as lowering blood pressure or killing cancerous cells.
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He struggles with what he has done; at the beginning of his incarceration, when, pharmacologically stabilized for the first time, he was suddenly lucid, he couldn't do anything but lie in bed and cry.
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And if she is correct that a certain ensemble of neurochemical events underlies the placebo effect, then what is to stop a drug company from manufacturing a drug — a real drug, that is — that activates the same process pharmacologically?
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Although both drugs are pharmacologically similar, the sentencing structure behind them was enormously disparate: You needed to have just 5 grams of crack to end up in prison for five years, compared to a requirement of 500 grams for powder cocaine.
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Since 1994, even herbs that contain clearly pharmacologically active substances are allowed to be sold over the counter without testing if they have previously been used medically—unless they are proven to be harmful and as long as they aren't claimed to cure or treat medical disorders.
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Pharmacologically reducing serotonin synthesis, and pharmacologically enhancing synaptic serotonin can produce and attenuate negative affective biases, respectively. These emotional processing biases may explain the therapeutic gap.
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Despite severe epithelial lesions, alveolar clearance is usually pharmacologically stimulable.
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This approach enables the membrane properties of the patch to be analysed pharmacologically.
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Metabolites may also be pharmacologically active, sometimes more so than the parent drug (see prodrug).
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M6 has less than one-fiftieth the potency of ivacaftor and is not considered pharmacologically active.
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Solanidine is a very important precursor for the synthesis of hormones and some pharmacologically active compounds.
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Lupeol is a pharmacologically active pentacyclic triterpenoid. It has several potential medicinal properties, like anticancer and anti-inflammatory activity.
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Megacystis can often be treated pharmacologically or with biofeedback to improve bladder functioning, if the child survives past early infancy.
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It is a racemic compound with two stereoisomers, the (S)-(–)-isomer being five times as pharmacologically active as the (R)-(+)-isomer.
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Azipramine (TQ-86) is a tetracyclic antidepressant (TeCA) which was synthesized and assayed pharmacologically in animals in 1976, but was never marketed.
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A common Phase I oxidation involves conversion of a C-H bond to a C-OH. This reaction sometimes converts a pharmacologically inactive compound (a prodrug) to a pharmacologically active one. By the same token, Phase I can turn a nontoxic molecule into a poisonous one (toxification). Simple hydrolysis in the stomach is normally an innocuous reaction, however there are exceptions.
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Volume of distribution is 1640L. Metabolism: Duloxetine undergoes predominately hepatic metabolism via two cytochrome P450 isozymes, CYP2D6 and CYP1A2. Circulating metabolites are pharmacologically inactive.
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All conorfamides are disulfide-poor conotoxins.Lebbe, E.K., Tygat J. (2016). In the picture: disulfide-poor conopeptides, a class of pharmacologically interesting compounds. J. Venom Anim.
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A chemical space often referred to in cheminformatics is that of potential pharmacologically active molecules. Its size is estimated to be in the order of 1060 molecules. There are no rigorous methods for determining the precise size of this space. The assumptions used for estimating the number of potential pharmacologically active molecules, however, use the Lipinski rules, in particular the molecular weight limit of 500.
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The prescription drug lovastatin, identical to monacolin K, is the principal statin produced by M. purpureus. Only the open-ring (hydroxy acid) form is pharmacologically active.
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Like its close relative theanine, it is a pharmacologically active constituent of green tea, with preliminary evidence for at least comparable activity to theanine as a hypotensive.
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Metralindole (Inkazan) is a reversible inhibitor of monoamine oxidase A (RIMA) which was investigated in Russia as a potential antidepressant. It is structurally and pharmacologically related to pirlindole.
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Pharmacologically active metabolite of diazepam, q.v. Prepn: S. C. Bell, (1965 to Am. Home. Prod.). See also: E. Reeder et al., and (1967, 1968, both to Hoffmann-La Roche).
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Lignans are under basic research for their potential anti-inflammatory or antioxidant activity in laboratory models of human diseases. Hinokinin is an emerging lignan with many pharmacologically useful properties.
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Results from a study at the University of Iowa indicate that it may have potential as an analgesic and as a therapeutic tool for treating drug addictions.Masis 2007-02-28 (US Media)Prisinzano, Tidgewell & Harding 2005. A pharmacologically important aspect of the contraction-reducing (antispasmodic) properties of ingested Salvinorin A on gut tissue is that it is only pharmacologically active on inflamed and not normal tissue, thus reducing possible side- effects.Capasso 2008.
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Corn silk contains a variety of pharmacologically-active compounds, and as such is used in many types of folk medicine, including as a diuretic and as an inhibitor of melanin production.
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Pirlindole (Lifril, Pyrazidol) is a reversible inhibitor of monoamine oxidase A (RIMA) which was developed and is used in Russia as an antidepressant. It is structurally and pharmacologically related to metralindole.
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Salvinorin A is capable of inhibiting excess intestinal motility (e.g. diarrhea), through its potent κ-opioid-activating effects. The mechanism of action for salvinorin A on ileal tissue has been described as 'prejunctional', as it was able to modify electrically induced contractions, but not those of exogenous acetylcholine. A pharmacologically important aspect of the contraction-reducing properties of ingested salvinorin A on gut tissue is that it is only pharmacologically active on inflamed and not normal tissue, thus reducing possible side-effects.
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Modulating the pyrimidine metabolism pharmacologically has therapeutical uses. Pyrimidine synthesis inhibitors are used in active moderate to severe rheumatoid arthritis and psoriatic arthritis, as well as in multiple sclerosis. Examples include Leflunomide and Teriflunomide.
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The Tetramorium bicarinatum's venom arrangement shows potential for a new pharmacologically active substance, bicarinalin. This antibacterial, antimicrobial, and anti-infective compound could potentially be chemically synthesized to combat antibiotic-resistant pathogens by means of drug therapy.
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Chemicals can have pharmacologically relevant properties and effects. Pharmacokinetics describes the effect of the body on the chemical (e.g. half-life and volume of distribution), and pharmacodynamics describes the chemical's effect on the body (desired or toxic).
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Those embryoid bodies are then pharmacologically treated with patterning factors to drive the formation of the desired organoid identity. Organoids have also been created using adult stem cells extracted from the target organ, and cultured in 3D media.
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The MRGPRX receptor is a possible therapeutic target and can be pharmacologically activated using a 48/80 agonist to control bacterial infection. It is also hypothesised that other QSMs and even Gram-negative bacterial signals can activate this receptor.
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Pindone is an anticoagulant drug for agricultural use. It is commonly used as a rodenticide in the management of rat and rabbit populations. It is pharmacologically analogous to warfarin and inhibits the synthesis of Vitamin K-dependent clotting factors.
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GHB is also produced as a result of fermentation and so is found in small quantities in some beers and wines, in particular fruit wines. The amount found in wine is pharmacologically insignificant and not sufficient to produce psychoactive effects.
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Bed bug secretions can inhibit the growth of some bacteria and fungi; antibacterial components from the bed bug could be used against human pathogens, and be a source of pharmacologically active molecules as a resource for the discovery of new drugs.
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Because cotinine is the main metabolite to nicotine and has been shown to be pharmacologically active, it has been suggested that some of nicotine's effects in the nervous system may be mediated by cotinine and/or complex interactions with nicotine itself.
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Ungeremine is a betaine-type alkaloid isolated from Nerine bowdenii and related plants such as Pancratium maritimum. Pharmacologically, it is of interest as an acetylcholinesterase inhibitor and accordingly as possibly relevant to Alzheimer's disease. It also has been investigated as a bactericide.
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Zuclopenthixol (brand names Cisordinol, Clopixol and others), also known as zuclopentixol, is a medication used to treat schizophrenia and other psychoses. It is classed, pharmacologically, as a typical antipsychotic. Chemically it is a thioxanthene. It is the cis-isomer of clopenthixol (Sordinol, Ciatyl).
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Dexchlorpheniramine (trade name Polaramine) is an antihistamine with anticholinergic properties used to treat allergic conditions such as hay fever or urticaria. It is the pharmacologically active dextrorotatory isomer of chlorpheniramine. It was patented in 1962 and came into medical use in 1959.
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Adverse effects may include seizures, coma, addiction, and an increased risk of suicide. Flashbacks may occur despite stopping usage. Chemically, PCP is a member of the arylcyclohexylamine class, and pharmacologically, it is a dissociative anesthetic. PCP works primarily as an NMDA receptor antagonist.
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All species produce five-petaled yellow flowers. The plants have a history of medicinal use in a variety of American cultures. Several pharmacologically active alkaloids have been detected in the plants. The generic names honours German physician Ernst Ludwig Heim (1747–1834).
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Pilocarpus is a genus of about 13 species of plants belonging to the family Rutaceae, native to the Neotropics of South America. Various species are important pharmacologically as a source of the parasympathomimetic alkaloid Pilocarpine. Many of the species have the common name jaborandi.
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Sofosbuvir is only administered orally. The peak concentration after oral administration is 0.5–2 hours post-dose, regardless of initial dose. Peak plasma concentration of the main circulating metabolite GS-331077 occurs 2–4 hours post-dose. GS-331077 is the pharmacologically inactive nucleoside.
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Phenaglycodol (brand names Acalmid, Acalo, Alterton, Atadiol, Felixyn, Neotran, Pausital, Remin, Sedapsin, Sinforil, Stesil, Ultran) is a drug described as a tranquilizer or sedative which has anxiolytic and anticonvulsant properties. It is related structurally and pharmacologically to meprobamate, though it is not a carbamate.
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HU-210 is a synthetic cannabinoid that was first synthesized in 1988 from (1R,5S)-myrtenolMechoulam, R., Lander, N., Breuer, A., Zahalka, J. Synthesis of the Individual, Pharmacologically Distinct, Enantiomers of a Tetrahydrocannabinol Derivative. Tetrahedron: Asymmetry. 1990. Vol 1, No 5. pp 315-318.
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Functionalized allylamines have extensive pharmaceutical applications. Pharmaceutically important allylamines include flunarizine and naftifine. Flunarizine aids in the relief of migraines while naftifine acts to fight common fungus causing infections such as athlete's foot, jock itch, and ringworm. Flunarizine and naftifine are pharmacologically active allylamines.
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The company derisks and repositions drugs using multidimensional profiles of pharmacologically relevant entities such as genes, diseases, drugs, pathways and cell types, to identify and rank potential adverse events and new indications for drugs in development, on the market, or generics. Biovista is also creating software-based tools and services for Reagent companies, researchers in the Life sciences and the consumer and patient health areas. Biovista's technology platform is based on the analysis and integration of Biomedical information available in the scientific literature using Biomedical text mining techniques. Pharmacologically-relevant areas include drug toxicity, drug mode of action, disease mechanisms and biological system interactions.
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Rapid sequence intubation refers to the pharmacologically induced sedation and neuromuscular paralysis prior to intubation of the trachea. The technique is a quicker form of the process normally used to induce general anesthesia. A useful framework for describing the technique of RSI is the "seven Ps".
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Modern knowledge of medicinal plants is being systematised in the Medicinal Plant Transcriptomics Database, which by 2011 provided a sequence reference for the transcriptome of some thirty species. The major classes of pharmacologically active phytochemicals are described below, with examples of medicinal plants that contain them.
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The frogs generate many different pharmacologically active peptides as part of the defensive secretions covering their skin. Several of these peptides have found scientific uses as research ligands, including the opioid peptide dermorphin.Bogdanich, W. and R. R. Ruiz. Turning to Frogs for Illegal Aid in Horse Races.
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Ivacaftor is extensively metabolised in humans. In vitro and in vivo data indicate that ivacaftor is primarily metabolised by CYP3A. M1 and M6 are the two major metabolites of ivacaftor in humans. M1 has approximately one-sixth the potency of ivacaftor and is considered pharmacologically active.
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The dried flower buds of Magnolia biondii are used medicinally in China and Japan. They are used to relieve coughing and nasal obstruction. Pharmacologically, five lignans including pinoresinol dimethyl ether, magnolin, epi-magnolin A, fargesin, and demethoxyaschantin have been attributed to the medicinal effect of Magnolia biondii.
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Urine is often the preferred specimen for routine drug abuse monitoring purposes. The presence of 7-aminoflunitrazepam, a pharmacologically-active metabolite and in vitro degradation product, is useful for confirmation of flunitrazepam ingestion. In postmortem specimens, the parent drug may have been entirely degraded over time to 7-aminoflunitrazepam.
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Chemical structure of lamotrigine Phenyltriazines are a class of molecules containing a phenyl group and a triazine group. These molecules are pharmacologically important. As an example, lamotrigine is a phenyltriazine derivative used as an anticonvulsant drug and has been shown to be useful for alleviating epilepsy and bipolar disorder.
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Dexbrompheniramine is an antihistamine with anticholinergic properties used to treat allergic conditions such as hay fever or urticaria. It is the pharmacologically active dextrorotatory isomer of brompheniramine. It was formerly marketed in combination with pseudoephedrine under the name Drixoral in the US and Canada. It is an alkylamine antihistamine.
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Because of the arrangement of the sucrose gap chambers, the technique of stimulating the neuron or cell is simple and reliable. This method is also useful in studying the changes in membrane potential in response to different pharmacologically active agents, which can be introduced in the test chamber.
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Stimulation by norepinephrine initially decreases blood flow to the salivary glands due to constriction of blood vessels but this effect is overtaken by vasodilation caused by various local vasodilators. Saliva production may also be pharmacologically stimulated by the so-called sialagogues. It can also be suppressed by the so-called antisialagogues.
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M1 possesses about of pharmacological activity of glimepiride, yet it is unknown if this results in clinically meaningful effect on blood glucose. M1 is further metabolized to M2 metabolite by cytosolic enzymes. M2 is pharmacologically inactive. Excretion in the urine is about 65%, and the remainder is excreted in the feces.
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Patients are also sometimes treated pharmacologically. To both induce menses and improve bone density, doctors may prescribe cyclic estrogen or progesterone as is used to treat post-menopausal women. Patients may also be put on oral contraceptives to stimulate regular periods. In addition to hormone therapy, nutrition supplements may be recommended.
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In the past 40 years, experiments have been carried out on the white sapote's seeds that have yielded the identity of many pharmacologically active compounds, including: N-methylhistamine, N,N-dimethylhistamine, and histamine. It also contains 2′,5,6-trimethoxyflavone, 2′, 6',5,6,-tetramethoxyflavone (zapotin), and 5-hydroxy-2′,6,7-trimethoxyflavone (zapotinin).
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Most NSAIDs are chiral molecules; diclofenac is a notable exception. However, the majority are prepared as racemic mixtures. Typically, only a single enantiomer is pharmacologically active. For some drugs (typically profens), an isomerase enzyme in vivo converts the inactive enantiomer into the active form, although its activity varies widely in individuals.
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In addition it has now been documented in the medical literature that one of the major metabolites of quazepam, N-desalkyl-2-oxoquazepam (N-desalkylflurazepam), which is long- acting and prone to accumulation, binds unselectively to benzodiazepine receptors, thus quazepam may not differ all that much pharmacologically from other benzodiazepines.
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Identification of human PDE7B, a cAMP-specific phosphodiesterase. Biochem Biophys Res Commun 271, 575-583. . There are 21 PDE genes in mammals that are pharmacologically-grouped into 11 families based on their biochemical characteristics and sequence conservation. The PDE7 family is composed of PDEs encoded by two genes, PDE7A and PDE7B.
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Tetrahydrocannabinol (THC) is one of at least 113 cannabinoids identified in cannabis. THC is the principal psychoactive constituent of cannabis. With chemical name (−)-trans-Δ⁹-tetrahydrocannabinol, the term THC also refers to cannabinoid isomers. Like most pharmacologically active secondary metabolites of plants, THC is a lipid found in cannabis,Firn, Richard (2010).
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GPCRs are pharmacologically important transmembrane proteins. Their X-ray crystal structures were revealed long after other transmembrane proteins of lesser interest. The difficulty in obtaining protein crystals of GPCRs was likely due to their high flexibility. Less flexible versions were obtained by truncating, mutating, and inserting T4 lysozyme in the recombinant sequence.
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165-71 Pharmacologically, Ichthammol has anti-inflammatory, bactericidal, and fungicidal properties. It is used to treat a variety of skin disorders as e.g. eczema, psoriasis, Acne rosacea and acne, and it decreases microorganisms in the area surrounding a skin condition. It is commonly used in 10% or 20% concentrate ointment, applied topically.
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During tests, there were no substantial changes in deep sleep; however, it may reduce REM sleep. In EEG tests of healthy volunteers, etizolam showed some similar characteristics to tricyclic antidepressants. Etizolam's main metabolites in humans are alpha- hydroxyetizolam and 8-hydroxyetizolam. Alpha-hydroxyetizolam is pharmacologically active and has a half-life of approximately 8.2 hours.
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In the Bandipora area, the dried rhizome was used to treat eczma and respiratory problems. It was also used to treat asthma, cancer, inflammation, liver and uterine diseases. It is medically important due to the pharmacologically active compounds (within the rhizome) including quinones, triterpenoids, flavonoids, isoflavonoids and stilbene glycosides. It can also treat animal ailments.
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The essential oils from Ocotea cymbarum are often used in the synthesis of MDMA (contracted from 3,4-methylenedioxy- methamphetamine); a psychoactive drug of the substituted methylenedioxyphenethylamine and substituted amphetamine classes of drugs that is consumed primarily for its euphoric and empathogenic effects. Pharmacologically, MDMA acts as a serotonin-norepinephrine-dopamine releasing agent and reuptake inhibitor.
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Plants For A Future: Tilia tomentosa, which cites Lauriault, J. (1989). Identification Guide to the Trees of Canada. Fitzhenry and Whiteside, Ontario. This may be attributable to the presence of pharmacologically active ligands of benzodiazepine receptor A widespread belief is that the nectar of this species contains mannose, which can be toxic to some bees.
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It exhibits a large diversity of bioactivities and shows properties such as anti-inflammatory, antifeedant and activation of bitter sensory receptors, but has not yet been used in medicine. Despite its pharmacologically beneficial properties, it can be toxic in higher doses. The compound has attracted attention in recent years as a potential anticancer drug.
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Since the root cause of anxiety is idiopathic, animal models are difficult to create and therefore flawed. But because changes are seen through administration of anxiolytic agents, they are pharmacologically proven. In the HBT studies show inconsistent results when administrating known anti-anxiety medication such as benzodiazepines. The HBT showing neophilia is also controversial.
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Bock created his own system of plant classification. Physician Valerius Cordus (1515–1544) authored a botanically and pharmacologically important herbal Historia Plantarum in 1544 and a pharmacopoeia of lasting importance, the Dispensatorium in 1546. Naturalist Conrad von Gesner (1516–1565) and herbalist John Gerard (1545–c. 1611) published herbals covering the medicinal uses of plants.
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Tiletamine is a dissociative anesthetic and pharmacologically classified as an NMDA receptor antagonist. It is related chemically to ketamine. Tiletamine hydrochloride exists as odorless white crystals. It is used in veterinary medicine in the combination product Telazol (tiletamine/zolazepam, 50 mg/ml of each in 5 ml vial) as an injectable anesthetic for use in cats and dogs.
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Many plants that grow in the American West have use in traditional and herbal medicine. Eriogonum fasciculatum, used in treatment of headaches and diarrhea. Dandelion (Taraxacum officinale) contains a large number of pharmacologically active compounds, and has been used for centuries as an effective laxative and diuretic, and as a treatment for bile or liver problems.
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Octreotide, sold under the brand name Sandostatin among others, is an octapeptide that mimics natural somatostatin pharmacologically, though it is a more potent inhibitor of growth hormone, glucagon, and insulin than the natural hormone. It was first synthesized in 1979, by the chemist Wilfried Bauer. It was approved for use in the United States in 1988.
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Mesuximide (or methsuximide, methosuximide) is a succinimide anticonvulsant medication. It is sold as a racemate by Pfizer under the tradenames Petinutin (Switzerland) and Celontin (United States). The therapeutic efficacy of methosuximide is largely due to its pharmacologically active metabolite, N-desmethylmethosuximide, which has a longer half-life and attains much higher plasma levels than its parent.
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Born researches and publishes in the field of memory formation during sleep. He was one of the first researchers to show that sleep was causally related to memory. He showed that procedural memories are not consolidated by REM sleep, as has been previously assumed. Instead, he showed that procedural memories are improved when REM sleep is pharmacologically suppressed.
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Moexipril is available as a prodrug moexipril hydrochloride, and is metabolized in the liver to form the pharmacologically active compound moexiprilat. Formation of moexiprilat is caused by hydrolysis of an ethyl ester group. Moexipril is incompletely absorbed after oral administration, and its bioavailability is low.Chrysant, George S, PK Nguyen. “Moexipril and left ventricular hypertrophy.” Vascular Health Risk Management.
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She found that optogenetically stimulating the ventrolateral subdivision of the ventromedial hypothalamus causes male mice to attack both male and female mice as well as inanimate objects. She also found that pharmacologically silencing these neurons prevented aggression and using in vivo electrophysiological recording she determined that these neurons are inhibited during mating. Lin completed her postdoctoral work in 2010.
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Azilsartan medoxomil is quickly absorbed from the gut, independently of food intake. Maximal blood plasma concentrations are reached after one to three hours. The liver enzyme CYP2C9 is involved in the formation of the two main metabolites, which are pharmacologically inactive; they are the O-deethylation and decarboxylation products of azilsartan. Elimination half life is about 11 hours.
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In 1990, Simons et al. isolated apocynin to a pharmacologically useful level using an actively guided isolation procedure. Apocynin's observed anti- inflammatory capabilities proved to be a result of its ability to selectively prevent the formation of free radicals, oxygen ions, and peroxides in the body. Apocynin has since been extensively studied to help determine its disease-fighting capabilities and applications.
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Saliva production may be pharmacologically stimulated by sialagogues such as pilocarpine and cevimeline. It can also be suppressed by so-called antisialagogues such as tricyclic antidepressants, SSRIs, antihypertensives, and polypharmacy. A Cochrane review found there was no strong evidence that topical therapies are effective in relieving the symptoms of dry mouth. Cancer treatments including chemotherapy and radiation therapy may impair salivary flow.
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Administering medication vaginally using an applicator. Administering medication vaginally without an applicator. Intravaginal administration is a route of administration where the substance is applied inside the vagina. Pharmacologically, it has the potential advantage to result in effects primarily in the vagina or nearby structures (such as the vaginal portion of cervix) with limited systemic adverse effects compared to other routes of administration.
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Some observational studies have detected significant associations between benzodiazepines and respiratory infections such as pneumonia where others have not. A large meta-analysis of pre-marketing randomized controlled trials on the pharmacologically related Z-Drugs suggest a small increase in infection risk as well. An immunodeficiency effect from the action of benzodiazepines on GABA-A receptors has been postulated from animal studies.
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The duration and intensity of pharmacological action of most lipophilic drugs are determined by the rate they are metabolized to inactive products. The Cytochrome P450 monooxygenase system is the most important pathway in this regard. In general, anything that increases the rate of metabolism (e.g., enzyme induction) of a pharmacologically active metabolite will decrease the duration and intensity of the drug action.
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Ticagrelor is absorbed quickly from the gut, the bioavailability being 36%, and reaches its peak concentration after about 1.5 hours. The main metabolite, AR-C124910XX, is formed quickly via CYP3A4 by de- hydroxyethylation at position 5 of the cyclopentane ring. It peaks after about 2.5 hours. Both ticagrelor and AR-C124910XX are bound to plasma proteins (>99.7%), and both are pharmacologically active.
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Those who have suffered from Hansen's disease describe the impact of social stigma as far worse than the physical manifestations despite it being only mildly contagious and pharmacologically curable. This sentiment is echoed by Weis and Ramakrishna, who noted that “the impact of the meaning of the disease may be a greater source of suffering than symptoms of the disease”.
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Once formed, MAC mediates the release of cytochrome c to the cytosol, triggering the commitment step of the mitochondrial apoptotic cascade. Depletion of MAC activity is accomplished pharmacologically by specific compounds, namely Bax channel inhibitors and MAC inhibitors. Either by knocking down MAC's main components or by its pharmacological inhibition, the end result is prevention of cytochrome c release and apoptosis.
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These attributes or molecular properties may either be determined empirically or computationally derived descriptors. One of the most popular clustering approaches is the Jarvis- Patrick algorithm . In pharmacologically oriented chemical repositories, similarity is usually defined in terms of the biological effects of compounds (ADME/tox) that can in turn be semiautomatically inferred from similar combinations of physico-chemical descriptors using QSAR methods.
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In addition to 4-HPA, the enzyme has been reported to have activity on a number of other phenolic substrates. Metabolic engineers have demonstrated that microbes expressing the E. coli enzyme can catalyze reactions such as hydroxylation of tyrosine to L-dopa and hydroxylation of the pharmacologically interesting phenylpropanoids umbelliferone and resveratrol. However, these approaches are not currently used commercially.
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The assumption that the test is based on conflict has been heavily criticized. Critics point out that when measuring anxiety each choice should have both positive and negative outcomes. This leads to more dependable observations which the OFT does not present. When the test was first developed, it was pharmacologically validated through the use of benzodiazepines, a common anxiety medication.
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Since conditions such as anxiety are idiopathic, animal models are difficult to create and therefore flawed. However animal models can be pharmacologically validated by usually by benzodiazepines, a common anti anxiety medication. Other drugs that are known to treat anxiety such as SSRIs which theoretically increase number of responses, show no effect in the VCT. The VCT can give false positives.
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Norcocaine is a minor metabolite of cocaine. It is the only confirmed pharmacologically active metabolite of cocaine, although salicylmethylecgonine is also speculated to be an active metabolite. The local anesthetic potential of norcocaine has been shown to be higher than that of cocaine, however cocaine continues to be more widely used. Norcocaine used for research purposes is typically synthesized from cocaine.
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Letrozole distributes rapidly around the body and is thoroughly distributed to tissues. Around 60% of the drug is bound to plasma proteins, especially albumin (55%). The elimination of letrozole is very slow and the elimination half-life is approximately 2 days. The main route of elimination of the drug is metabolism in the liver to the pharmacologically inactive metabolite carbinol.
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External medications will affect the cost benefits advantages of deploying an evolved self-treatment. Some animals use external ones. Wild animals, including apes, do so in the form of ingested detoxifying clays, rough leaves that clear gut parasites, and pharmacologically active plants Complementary to this, research finds that animals have the ability to select and prefer substances that aid their recuperation from illness.
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Erdosteine is a molecule with mucolytic activity. Structurally is a thiol derivative characterized by the presence of two thiol groups. These two functional sulfhydryl groups contained in the molecule are released following first-pass metabolism with the conversion of erdosteine into its pharmacologically active metabolite Met-I. In Italy the drug is used as mucolytic and fluidifying for chronic and acute respiratory disorders.
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PhTX-433 was structurally elucidated and synthesized in 1988 by Eldefrawi and colleagues. For the isolation and structural identification of PhTX-433 female wasp venom glands were fractionated using reverse-phase HPLC and fractions were tested for pharmacological activity. The most pharmacologically active sample was re- fractioned using the same method. UV spectrum and H1NMR analysis revealed that the structure consisted of a butyrl/tyrosil/polyamine sequence.
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Meanwhile, geneticists and molecular biologists have characterised five genes that appear to encode muscarinic receptors, named m1-m5 (lowercase m; no subscript number). The first four code for pharmacologic types M1-M4. The fifth, M5, corresponds to a subtype of receptor that had until recently not been detected pharmacologically. The receptors m1 and m2 were determined based upon partial sequencing of M1 and M2 receptor proteins.
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Clonazepam is lipid- soluble, rapidly crosses the blood–brain barrier, and penetrates the placenta. It is extensively metabolised into pharmacologically inactive metabolites, with only 2% of the unchanged drug excreted in the urine. Clonazepam is metabolized extensively via nitroreduction by cytochrome P450 enzymes, including CYP3A4. Erythromycin, clarithromycin, ritonavir, itraconazole, ketoconazole, nefazodone, cimetidine, and grapefruit juice are inhibitors of CYP3A4 and can affect the metabolism of benzodiazepines.
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Apart from acetylcholine, adrenaline and noradrenaline were the first neurotransmitters to be discovered and the first intercellular biochemical signals to be found in intracellular vesicles. The β-adrenoceptor was the first G protein-coupled receptor the gene of which was cloned. Goal-directed catecholamine research began with the preparation by George Oliver and Edward Albert Sharpey-Schafer of a pharmacologically active extract from the adrenal glands.
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Common names include Pacific Coast mahogany, caoba del Pacifico, caoba del Honduras, caobilla, cobano, gateado, sopilocuahuilt, venadillo and zapaton. In the wood trades it is known as Honduras mahogany and Mexican mahogany. The tree has been over-exploited for its wood which is valuable for making furniture. The plant also is of interest as a possibly commercial source of seed oil and pharmacologically active compounds.
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Different benzodiazepine drugs have different side groups attached to this central structure. The different side groups affect the binding of the molecule to the GABAA receptor and so modulate the pharmacological properties. Many of the pharmacologically active "classical" benzodiazepine drugs contain the 5-phenyl-1H-benzo[e] [1,4]diazepin-2(3H)-one substructure (see figure to the right).CAS registry number:; other names: Ro 05-2921, dechlorodemethyldiazepam.
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Carbonyl reductase [NADPH] 3 is an enzyme that in humans is encoded by the CBR3 gene. Carbonyl reductase 3 catalyzes the reduction of a large number of biologically and pharmacologically active carbonyl compounds to their corresponding alcohols. The enzyme is classified as a monomeric NADPH- dependent oxidoreductase. CBR3 contains three exons spanning 11.2 kilobases and is closely linked to another carbonyl reductase gene - CBR1.
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Moracizine, a phenothiazine derivative, undergoes extensive first-pass metabolism and is also extensively metabolized after it has entered the circulation. It may have pharmacologically active metabolites. A clinical study has shown that moracizine is slightly less effective than encainide or flecainide in suppressing ventricular premature depolarizations. Compared with disopyramide and quinidine, moracizine was equally or more effective in suppressing premature ventricular contractions, couplets, and nonsustained ventricular tachycardia.
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Arrhythmias may also be treated electrically, by applying a shock across the heart — either externally to the chest wall, or internally to the heart via implanted electrodes. Cardioversion is either achieved pharmacologically or via the application of a shock synchronised to the underlying heartbeat. It is used for treatment of supraventricular tachycardias. In elective cardioversion, the recipient is usually sedated or lightly anesthetized for the procedure.
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BL-1020 (perphenazine 4-aminobutanoate) is an investigational orally-active antipsychotic for the possible treatment of schizophrenia, it's an ester of GABA and perphenazine, and pharmacologically it acts as a D2 antagonist and GABA agonist. It has shown pro-cognitive effects in the trials. In March 2013, it went into the II/III trial phase. It has been introduced by BioLineRx, a biopharmaceutical development company.
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Young's research career includes many highlights. In 1974 she published a paper contributing to the discovery of glutamate as a neurotransmitter. Additionally, a 1989 paper she co-authored describing an anatomically and pharmacologically derived model of basal ganglia disorders has been cited over 5000 times. As part of the Huntington Study Group, Young has published multiple reviews about the progress of research on Huntington's Disease.
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As with psilocybin, miprocybin and metocybin, ethocybin is a prodrug that is converted into the pharmacologically active compound ethocin in the body by dephosphorylation. This chemical reaction takes place under strongly acidic conditions or enzymatically by phosphatases in the body. Albert Hofmann was the first to produce this chemical, soon after his discovery of psilocin and psilocybin. It was sold under the code name CEY-39.
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The literature dealing with the pharmacologically-related properties of tetraethylammonium is vast, and research continues.There are over 8500 citations in PubMed, as of October 2012. It is clear that TEASince tetraethylammonium is always paired with an anion, the TEA salts, TEA chloride, TEA bromide, or TEA iodide have actually been used, but not always specified as such. Here, the term "TEA" is written for convenience.
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A prodrug is a medication or compound that, after administration, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be used to improve how the drug is absorbed, distributed, metabolized, and excreted (ADME). Prodrugs are often designed to improve bioavailability when a drug itself is poorly absorbed from the gastrointestinal tract.
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For one set, 99mTc MIBI is injected while the patient is at rest and then the myocardium is imaged. In the second set, the patient is stressed either by exercising on a treadmill or pharmacologically. The drug is injected at peak stress and then imaging is performed. The resulting two sets of images are compared with each other to distinguish ischemic from infarcted areas of the myocardium.
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TVOR is typically performed after ovarian hyperstimulation, where oocytes are pharmacologically stimulated to mature. When the ovarian follicles have reached a certain degree of development, induction of final oocyte maturation is performed, generally by an intramuscular or subcutaneous injection of human chorionic gonadotropin (hCG). TVOR is typically performed 3436 hours after hCG injection, when the eggs are fully mature but just prior to rupture of the follicles.
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There is also enzymatic degradation of the catecholamines by two main enzymes - monoamine oxidase and catechol-o-methyl transferase. Respectively, these enzymes oxidise monoamines (including catecholamines) and methylate the hydroxal groups of the phenyl moiety of catecholamines. These enzymes can be targeted pharmacologically. Inhibitors of these enzymes act as indirect agonists of adrenergic receptors as they prolong the action of catecholamines at the receptors.
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Cannabis cofactors have also been linked to lowering body temperature, modulating immune function, and cell protection. The essential oil of cannabis contains many fragrant terpenoids which may synergize with the cannabinoids to produce their unique effects. THC is converted rapidly to 11-hydroxy-THC, which is also pharmacologically active, so the euphoria outlasts measurable THC levels in blood. THC and cannabidiol are neuroprotective antioxidants.
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The molecule has three asymmetric carbon atoms, allowing for 23 = 8 stereomers. The trans stereomers are known to be pharmacologically active, but only the RRR-form is contained in the marketed formulation. The SRR-form (with the hydroxyl group in S configuration) is a minor metabolite that is formed in the human body, mainly in poor metabolizers. The infusion contains vernakalant hydrochloride, which is highly water soluble.
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In animal studies, the drug was quickly and nearly completely absorbed from the gut. Intake of food delays absorption, but it is not known whether this is clinically relevant. Ulipristal acetate is metabolized in the liver, most likely by CYP3A4, and to a small extent by CYP1A2 and CYP2D6. The two main metabolites have been shown to be pharmacologically active, but less than the original drug.
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Brilliant Blue FCF is an approved food colorant and pharmacologically inactive substance for drug formulations in the EU and the United States. It is also legal in other countries. It has the capacity for inducing allergic reactions in individuals with pre-existing moderate asthma. In 2003, the U.S. FDA issued a public health advisory to warn health care providers of the potential toxicity of this synthetic dye in enteral feeding solutions.
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2,3-Dichlorophenylpiperazine (2,3-DCPP or DCPP) is a chemical compound from the phenylpiperazine family. It is both a precursor in the synthesis of aripiprazole and one of its metabolites. It is unclear whether 2,3-DCPP is pharmacologically active as a serotonin receptor agonist similar to its close analogue 3-chlorophenylpiperazine (mCPP), though it has been shown to act as a partial agonist of the dopamine D2 and D3 receptors.
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Medically significant spider venoms include various combinations and concentrations of necrotic agents, neurotoxins, and pharmacologically active compounds such as serotonin. Worldwide only two spider venoms have impact on humans—those of the widow and recluse spiders. Unlike snake and scorpion envenomation, widow and recluse species bites rarely have fatal consequences. However, isolated spider families have a lethal neurotoxic venom: the wandering spider in Brazil and the funnel web in Australia.
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Elinogrel (INN, USAN) was an experimental antiplatelet drug acting as a P2Y12 inhibitor. Similarly to ticagrelor and in contrast to clopidogrel, elinogrel was a reversible inhibitor that acted fast and short (for about 12 hours), and it was not a prodrug but pharmacologically active itself. The substance was used in form of its potassium salt, intravenously for acute treatment and orally for long-term treatment. Development was terminated in 2012.
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In pharmacology and medicine vectorization of drugs refers to (intracellular) targeting with plastic, noble metal or silicon nanoparticles or liposomes to which pharmacologically active substances are reversibly bound or attached by adsorption. CNRS researchers have devised a way to overcome the problem of multidrug resistance using polyalkylcyanoacrylate (PACA) nanoparticles as "vectors". Drug nanocarriers are expected to play a major role in delivering multiple drugs to tumor tissues by overcoming biological barriers.
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Many plants produce chemical compounds for defence against herbivores. These are often useful as drugs, and the content and known pharmacological activity of these substances in medicinal plants is the scientific basis for their use. The major classes of pharmacologically active phytochemicals are described below, with examples of medicinal plants that contain them. Human settlements are often surrounded by weeds useful as medicines, such as nettle, dandelion and chickweed.
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Herb-drug interactions are drug interactions that occur between herbal medicines and conventional drugs. These types of interactions may be more common than drug- drug interactions because herbal medicines often contain multiple pharmacologically active ingredients, while conventional drugs typically contain only one. Some such interactions are clinically significant, although most herbal remedies are not associated with drug interactions causing serious consequences. Most herb-drug interactions are moderate in severity.
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Monoglycerides are produced both biologically and industrially. They are naturally present at very low levels (0.1-0.2%) in some seed oils such as olive oil, rapeseed oil and cottonseed oil. They are biosynthesized by the enzymatic hydrolysis of triglycerides by lipoprotein lipase and the enzymatic hydrolysis of diglycerides by diacylglycerol lipase; or as an intermediate in the alkanoylation of glycerol to form fats. Several monoglycerides are pharmacologically active (e.g.
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Both of these intramolecular and intermolecular reactions are used for the artificial synthesis of various natural products and pharmacologically active compounds, as the reaction of a carboxylic acid with an amine produces an amide or a peptide. In acidic reactions, Lewis acid catalysts, such as metal triflates, exhibit high activities, while in basic reactions, 4-dimethylaminopyridine (DMAP), 4-dimethylaminopyridine N-oxide (DMAPO), and 4-pyrrolidinopyridine (PPY) are employed.
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Vigabatrin is an irreversible mechanism-based inhibitor of gamma-aminobutyric acid aminotransferase (GABA-AT), the enzyme responsible for the catabolism of GABA. Inhibition of GABA-AT results in increased levels of GABA in the brain. Vigabatrin is a racemic compound, and its [S]-enantiomer is pharmacologically active., Crystal Structure (pdb:1OHW) showing vigabatrin binding to specific residues in the active site of GABA-AT, based on experiments by Storici et al.
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1550 BC, describes over 850 plant medicines. The Greek physician Dioscorides, who worked in the Roman army, documented over 1000 recipes for medicines using over 600 medicinal plants in De materia medica, c. 60 AD; this formed the basis of pharmacopoeias for some 1500 years. Drug research makes use of ethnobotany to search for pharmacologically active substances in nature, and has in this way discovered hundreds of useful compounds.
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Compounds begin to break down as soon as they enter the body. The majority of small- molecule drug metabolism is carried out in the liver by redox enzymes, termed cytochrome P450 enzymes. As metabolism occurs, the initial (parent) compound is converted to new compounds called metabolites. When metabolites are pharmacologically inert, metabolism deactivates the administered dose of parent drug and this usually reduces the effects on the body.
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Cytosolic and membrane- bound forms of glutathione S-transferase are encoded by two distinct supergene families. These enzymes are involved in cellular defense against toxic, carcinogenic, and pharmacologically active electrophilic compounds. At present, eight distinct classes of the soluble cytoplasmic mammalian glutathione S-transferases have been identified: alpha, kappa, mu, omega, pi, sigma, theta and zeta. This gene encodes a glutathione S-transferase belonging to the alpha class.
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Tolerance to psilocybin builds and dissipates quickly; ingesting psilocybin more than about once a week can lead to diminished effects. Tolerance dissipates after a few days, so doses can be spaced several days apart to avoid the effect. A cross- tolerance can develop between psilocybin and the pharmacologically similar LSD, and between psilocybin and phenethylamines such as mescaline and DOM. Repeated use of psilocybin does not lead to physical dependence.
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ESP15228, the (also) active metabolite Following oral intake, bempedoic acid reaches highest blood plasma concentrations after 3.5 hours. Food does not affect its absorption. When in the bloodstream, 99.3% of the substance are bound to plasma proteins. About a fifth of the substance is reversibly converted by an aldo-keto reductase enzyme to a metabolite (called ESP15228) that is also pharmacologically active in form of its coenzyme A–thioester.
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The substance is mainly metabolized by CYP3A4, and to a lesser extent by CYP2D6 and CYP2C9. The main metabolites are desmethyl-netupitant (M1), netupitant N-oxide (M2), and hydroxy-netupitant (M3); all three are pharmacologically active. Netupitant and its metabolites are mainly excreted via the faeces. Biological half-life is 88 hours, significantly longer than that of the first NK1 receptor antagonist, aprepitant, which has a half-life of 9 to 13 hours.
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The elimination half-life of clozapine is about 14 hours at steady state conditions (varying with daily dose). Clozapine is extensively metabolized in the liver, via the cytochrome P450 system, to polar metabolites suitable for elimination in the urine and feces. The major metabolite, norclozapine (desmethyl-clozapine), is pharmacologically active. The cytochrome P450 isoenzyme 1A2 is primarily responsible for clozapine metabolism, but 2C, 2D6, 2E1 and 3A3/4 appear to play roles as well.
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Pharmacologically and chemically unrelated to SSRIs, the past four decades, norepinephrine has been asserted to play an important, possibly primary, role in the treatment of mental disorders. This was from the notion that depression was primarily due to norepinephrine deficits, partly based on the fact that drugs that relieve depression increase brain norepinephrine levels. To date, a great number of potent and selective (also mixed) NET inhibitors, e.g. selective NRIs, have been marketed as antidepressants.
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Liothyronine is the most potent form of thyroid hormone. As a salt of triiodothyronine (T3), it is chemically similar and pharmacologically equivalent to T3. As such, it acts on the body to increase the basal metabolic rate, affect protein synthesis and increase the body's sensitivity to catecholamines (such as adrenaline) by permissiveness. As monotherapy or in combination therapy with SSRIs, liothyronine may also enhance generation of new neurons in the central nervous system.
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Lupin poisoning is a nervous syndrome caused by alkaloids in bitter lupins. Lupin poisoning affects people who eat incorrectly prepared lupin beans. Mediterranean cultures prefer the historic bitter lupin beans with the required toxin-removal by traditional leaching in water preparation methods due to the better flavour that results. Improper preparation of bitter lupins with insufficient soaking allows pharmacologically significant amounts of the anticholinergic alkaloids to remain in the beans, and poisoning symptoms result.
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High affinity cAMP-specific 3',5'-cyclic phosphodiesterase 7A is an enzyme that in humans is encoded by the PDE7A gene. Mammals possess 21 cyclic nucleotide phosphodiesterase (PDE) genes that are pharmacologically grouped into 11 families. PDE7A is one of two genes in the PDE7 family, the other being PDE7B. The PDE7 family, along with the PDE4 and PDE8 families, are cAMP- specific, showing little to no activity against 3', 5'-cyclic guanosine monophosphate (cGMP).
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Oxcarbazepine is a prodrug, which is largely metabolised to its pharmacologically active 10-monohydroxy derivative licarbazepine (sometimes abbreviated MHD). Oxcarbazepine and MHD exert their action by blocking voltage-sensitive sodium channels, thus leading to the stabilization of hyper- excited neural membranes, suppression of repetitive neuronal firing and diminishment propagation of synaptic impulses. Furthermore, anticonvulsant effects of these compounds could be attributed to enhanced potassium conductance and modulation of high-voltage activated calcium channels.
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Glutathione S-transferase A3 is an enzyme that in humans is encoded by the GSTA3 gene. Cytosolic and membrane-bound forms of glutathione S-transferase are encoded by two distinct supergene families. These enzymes are involved in cellular defense against toxic, carcinogenic, and pharmacologically active electrophilic compounds. At present, eight distinct classes of the soluble cytoplasmic mammalian glutathione S-transferases have been identified: alpha, kappa, mu, omega, pi, sigma, theta and zeta.
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Meclizine is a first-generation antihistamine (nonselective H1 antagonist) of the piperazine class. It is structurally and pharmacologically similar to buclizine, cyclizine, and hydroxyzine, but has a shorter half-life of six hours compared to cyclizine and hydroxyzine with about 20 hours (though half-life should not be confused with duration). It is used as an antivertigo/antiemetic agent, specifically in the prevention and treatment of nausea, vomiting, and dizziness associated with motion sickness.Clinical Pharmacology.
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Bioavailability following subcutaneous and intramuscular injection in humans is high and similar for the two routes of administration (71% and 66%, respectively). Calcitonin has short absorption and elimination half-lives of 10–15 minutes and 50–80 minutes, respectively. Salmon calcitonin is primarily and almost exclusively degraded in the kidneys, forming pharmacologically inactive fragments of the molecule. Therefore, the metabolic clearance is much lower in patients with end-stage kidney failure than in healthy subjects.
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Tolerance is associated with the superactivation of the receptor, which may be affected by the degree of endocytosis caused by the opioid administered, and leads to a superactivation of cyclic AMP signaling. Long-term use of morphine in palliative care and the management of chronic pain always entails a risk that the patient develops tolerance or physical dependence. There are many kinds of rehabilitation treatment, including pharmacologically based treatments with naltrexone, methadone, or ibogaine.
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In an Affilin protein comprising two modified ubiquitin molecules, for example, up to 14 amino acids are exchanged, resulting in 8 × 1017 combinations, but not all of these are realized in a given library. The next step is the selection of Affilin proteins that bind the desired target protein. To this end display techniques such as phage display or ribosome display are used. The fitting species are isolated and characterized physically, chemically and pharmacologically.
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Ventral pallidum firing is also elevated by stress induced depression, an effect that is pharmacologically valid, and silencing of these neurons alleviates behavioral correlates of depression. Tentative in vivo evidence from people with MDD suggests abnormalities in dopamine signalling. This led to early studies investigating VTA activity and manipulations in animal models of depression. Massive destruction of VTA neurons enhances depressive behaviors, while VTA neurons reduce firing in response to chronic stress.
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Under therapy, normal bone tissue develops, and alendronate is deposited in the bone-matrix in a pharmacologically inactive form. For optimal action, enough calcium and vitamin D are needed in the body in order to promote normal bone development. Hypocalcemia should, therefore, be corrected before starting therapy. Etidronate has the same disadvantage as pyrophosphate in inhibiting mineralization, but all of the potent N-containing bisphosphonates, including alendronate, risedronate, ibandronate, and zoledronate, do not.
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Near the head and foot of the shaman was a large leather basket and wooden bowl filled with 789g of cannabis, superbly preserved by climatic and burial conditions. An international team demonstrated that this material contained tetrahydrocannabinol, the psychoactive component of cannabis. The cannabis was presumably employed by this culture as a medicinal or psychoactive agent, or an aid to divination. This is the oldest documentation of cannabis as a pharmacologically active agent.
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Four isomers of methylphenidate are possible, since the molecule has two chiral centers. One pair of threo isomers and one pair of erythro are distinguished, from which primarily d-threo-methylphenidate exhibits the pharmacologically desired effects. The erythro diastereomers are pressor amines, a property not shared with the threo diastereomers. When the drug was first introduced it was sold as a 4:1 mixture of erythro:threo diastereomers, but it was later reformulated to contain only the threo diastereomers.
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Krayer's main area of research was the pharmacology of the human heart and blood circulation. For instance, he pharmacologically characterised the ingredients of the Veratrum plant, such as veratramine. While working in Berlin, he cooperated with Wilhelm Feldberg to prove that acetylcholine is a neurotransmitter for the parasympathetic nervous system in mammals. This research was published in 1933 and that same year both researchers left Germany: Feldberg, who was Jewish, on 7 July, Otto Krayer on 31 December.
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The main metabolite in humans, which is pharmacologically inactive. Accessed 2020-07-30. The route of administration has only a slight effect on the drug's concentrations in the bloodstream: when given as an intramuscular injection, its bioavailability is 90% (as compared to the 100% availability when given directly into a vein), and its highest concentrations in the blood plasma are reached after about 2.3 hours. In the blood, 85–95% of ertapenem are bound to plasma proteins, mostly albumin.
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Intriguingly, enhancing inhibitory transmission pharmacologically in adult mice had no effect on neural circuit balance nor multisensory integration. Their finding suggests that enhancing inhibitory transmission during a critical developmental period can restore inhibitory/excitatory balance and restore normal multisensory integration functions of the IC. Gogolla's research, published in Neuron in 2014, received a large amount of attention due to the new insights in provided in how ASD might manifest in the human brain and lead to ASD type behaviors.
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Quinupramine (brand names Kevopril, Kinupril, Adeprim, Quinuprine) is a tricyclic antidepressant (TCA) used in Europe for the treatment of depression. Pharmacologically, quinupramine acts in vitro as a strong muscarinic acetylcholine receptor antagonist (anticholinergic) and H1 receptor antagonist (antihistamine), moderate 5-HT2 receptor antagonist, and weak serotonin and norepinephrine reuptake inhibitor. It has negligible affinity for the α1-adrenergic, α2-adrenergic, β-adrenergic, or D2 receptor. Clinically, quinupramine is reported to be stimulating similarly to imipramine, desipramine, and demexiptiline.
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Plants do not carry pathogens that might be dangerous to human health. Additionally, on the level of pharmacologically active proteins, there are no proteins in plants that are similar to human proteins. On the other hand, plants are still sufficiently closely related to animals and humans that they are able to correctly process and configure both animal and human proteins. Their seeds and fruits also provide sterile packaging containers for the valuable therapeutics and guarantee a certain storage life.
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Absorption by any administered route and the risk of accumulation is significantly increased in the neonate, and withdrawal of diazepam during pregnancy and breast feeding is clinically justified. Diazepam undergoes oxidative metabolism by demethylation (CYP 2C9, 2C19, 2B6, 3A4, and 3A5), hydroxylation (CYP 3A4 and 2C19) and glucuronidation in the liver as part of the cytochrome P450 enzyme system. It has several pharmacologically active metabolites. The main active metabolite of diazepam is desmethyldiazepam (also known as nordazepam or nordiazepam).
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Levamlodipine (INN), also known as levoamlodipine or S-amlodipine is a pharmacologically active enantiomer of amlodipine. Amlodipine belongs to the dihydropyridine group of calcium channel blocker used as an antihypertensive and antianginal agent. Levamlodipine is currently marketed in Russia under the brand name EsCordi Cor (Actavis Pharma), in Brazil under the brand name Novanlo (Biolab Sanus) and in India under the trade names Eslo (Zuventus Healthcare Ltd.), Asomex (Emcure Pharmaceutical Ltd.), and Espin (Intas Pharmaceuticals Ltd.).
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Flunoxaprofen is pharmacologically activated through biotransformation of the R-enantiomer to the S-enantiomer. This highly stereoselective chiral inversion is mediated by the FLX-S-Acyl-CoA thioester. Pharmacokinetic studies have been carried out by determining the level of propranolol enantiomers in the plasma after administering the racemic drug orally. It has been shown that the dextrorotatory form is particularly active and has a much higher therapeutic index than some other anti-inflammatories, including indomethacin and diclofenac.
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The R-enantiomer undergoes extensive interconversion to the S-enantiomer in vivo. The S-enantiomer is believed to be the more pharmacologically active enantiomer. The R-enantiomer is converted through a series of three main enzymes. These enzymes include acyl-CoA-synthetase, which converts the R-enantiomer to (-)-R-ibuprofen I-CoA; 2-arylpropionyl-CoA epimerase, which converts (-)-R-ibuprofen I-CoA to (+)-S-Ibuprofen I-CoA; and hydrolase, which converts (+)-S-ibuprofen I-CoA to the S-enantiomer.
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Several FLT3 inhibitors have undergone clinical trials, with mixed results. Two other mutations – NPM1 and biallelic CEBPA are associated with improved outcomes, especially in people with normal cytogenetics and are used in current risk stratification algorithms. Researchers are investigating the clinical significance of c-KIT mutations in AML. These are prevalent, and potentially clinically relevant because of the availability of tyrosine kinase inhibitors, such as imatinib and sunitinib that can block the activity of c-KIT pharmacologically.
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Acecainide is pharmacologically active as an antiarrhythmic agent. It has electrophysiological effects of a class III antiarrhythmic drug and it is used as a medicine to increase the Q – T interval of the PQRST heart rhythm in patients with cardiac arrhythmias. The equivalent drug procainamide, which is a class Ia antiarrhythmic drug, is also used in patients with cardiac arrhythmias. Nevertheless, NAPA does only affect the Q - T interval, while procainamide has also effect on the QRS-interval.
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Bear bile and gallbladders, which store bile, are ingredients in traditional Chinese medicine (TCM). Its first recorded use is found in Tang Ban Cao (Newly Revised Materia Medica, Tang Dynasty, 659 CE). The pharmacologically active ingredient contained in bear bile and gallbladders is ursodeoxycholic acid (UDCA); bears are the only mammals to produce significant amounts of UDCA. Initially, bile was collected from wild bears which were killed and the gall and its contents cut from the body.
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Evans blue is also used to assess the permeability of the blood–brain barrier to macromolecules. Because serum albumin cannot cross the barrier and virtually all Evans blue is bound to albumin, normally the neural tissue remains unstained. When the blood–brain barrier has been compromised, albumin-bound Evans blue enters the CNS. Evans blue is pharmacologically active, acting as a negative allosteric modulator of the AMPA and kainate receptors and as an inhibitor of vesicular glutamate transporters.
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Lorazepam has anxiolytic, sedative, hypnotic, amnesic, anticonvulsant, and muscle relaxant properties. It is a high-potency and an benzodiazepine, and its uniqueness, advantages, and disadvantages are largely explained by its pharmacokinetic properties (poor water and lipid solubility, high protein binding and anoxidative metabolism to a pharmacologically inactive glucuronide form) and by its high relative potency (lorazepam 1 mg is equal in effect to diazepam 10 mg). The biological half-life of lorazepam is 10–20 hours.
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Other attempts to modulate the G2/M transition for chemotherapy applications have focused on the DNA damage checkpoint. Pharmacologically bypassing the G2/M checkpoint via inhibition of Chk1 has been shown to enhance cytotoxicity of other chemotherapy drugs. Bypassing the checkpoint leads to the rapid accumulation of deleterious mutations, which is thought to drive the cancerous cells into apoptosis. Conversely, attempts to prolong the G2/M arrest have also been shown to enhance the cytotoxicity of drugs like doxorubicin.
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Ractopamine is an animal feed additive used to promote leanness and increase food conversion efficiency in livestock in some countries, but banned in others. Pharmacologically, it is a phenol-based TAAR1 agonist and β adrenoreceptor agonist that stimulates β1 and β2 adrenergic receptors. It is most commonly administered to animals for meat production as ractopamine hydrochloride. It is the active ingredient in products marketed in the US as Paylean for swine, Optaflexx for cattle, and Topmax for turkeys.
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Alendronate inhibits osteoclast-mediated bone-resorption. Like all bisphosphonates, it is chemically related to inorganic pyrophosphate, the endogenous regulator of bone turnover. But while pyrophosphate inhibits both osteoclastic bone resorption and the mineralization of the bone newly formed by osteoblasts, alendronate specifically inhibits bone resorption without any effect on mineralization at pharmacologically achievable doses. Its inhibition of bone-resorption is dose-dependent and approximately 1,000 times stronger than the equimolar effect of the first bisphosphonate drug, etidronate.
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Aniracetam has been shown to positively modulate the AMPA receptor. When ingested orally aniracetam is quickly broken down via first pass hepatic metabolism. The primary metabolites of aniracetam are N-anisoyl-GABA, (70–80%), 2-Pyrrolidinone and p-anisic acid (20–30%). Plasma concentrations are generally in the 5–15 μg/L range for aniracetam and 5–15 mg/L range for N-anisoyl-GABA, a pharmacologically-active metabolite, during the first few hours after oral administration of the drug.
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Transaction Publishers; 1998. . p. 178–. Their existence is impossible to falsify, and ghost hunting has been classified as pseudoscience. Despite centuries of investigation, there is no scientific evidence that any location is inhabited by spirits of the dead. Historically, certain toxic and psychoactive plants (such as datura and hyoscyamus niger), whose use has long been associated with necromancy and the underworld, have been shown to contain anticholinergic compounds that are pharmacologically linked to dementia (specifically DLB) as well as histological patterns of neurodegeneration.
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Atipamezole is a veterinary drug whose prime purpose is to reverse the effects of the sedative dexmedetomidine (as well as its racemic mixture, medetomidine).Because dexmedetomidine is the only pharmacologically active component of medetomidine, they will both be referred to as dexmedetomidine from here on out. It can also be used to reverse the related sedative xylazine. While it reverses both the sedative and analgesic (pain-relieving) effects of dexmedetomidine, atipamezole may not entirely reverse the cardiovascular depression that dexmedetomidine causes.
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The opioid analgesic drug morphine is a natural product derived from the plant Papaver somniferum. Plants are a major source of complex and highly structurally diverse chemical compounds (phytochemicals), this structural diversity attributed in part to the natural selection of organisms producing potent compounds to deter herbivory (feeding deterrents). Major classes of phytochemical include phenols, polyphenols, tannins, terpenes, and alkaloids. Though the number of plants that have been extensively studied is relatively small, many pharmacologically active natural products have already been identified.
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McGraw Hill Education. Due to its embarrassing nature and the shame felt by sufferers, the subject was taboo for a long time, and is the subject of many urban legends. Folk remedies have long been advocated, with some being advertised widely since the 1930s. The introduction of perhaps the first pharmacologically effective remedy for impotence, sildenafil (trade name Viagra), in the 1990s caused a wave of public attention, propelled in part by the news-worthiness of stories about it and heavy advertising.
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The pharmacologically inert cysteine adduct subsequently undergoes ester hydrolysis and the by-products are eliminated via renal and/or hepatic mechanisms. Unlike the pH- and temperature-dependent chemodegradation seen with atracurium and cisatracurium, the inactivation of gantacurium via cysteine adduct formation is independent of body pH and temperature. The use of extrinsically administered cysteine to deliberately accelerate reversal of the pharmacological effect of fumarate bis-onium neuromuscular blocking drugs (RV002 [formerly known as AV002], CW002 and CW011) is being investigated currently.
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From ancient times to the present, Ayurvedic medicine as documented in the Atharva Veda, the Rig Veda and the Sushruta Samhita has used hundreds of pharmacologically active herbs and spices such as turmeric, which contains curcumin. The Chinese pharmacopoeia, the Shennong Ben Cao Jing records plant medicines such as chaulmoogra for leprosy, ephedra, and hemp. This was expanded in the Tang Dynasty Yaoxing Lun. In the fourth century BC, Aristotle's pupil Theophrastus wrote the first systematic botany text, Historia plantarum.
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The place of plants in medicine was radically altered in the 19th century by the application of chemical analysis. Alkaloids were isolated from a succession of medicinal plants, starting with morphine from the poppy in 1806, and soon followed by ipecacuanha and strychnos in 1817, quinine from the cinchona tree, and then many others. As chemistry progressed, additional classes of pharmacologically active substances were discovered in medicinal plants. Commercial extraction of purified alkaloids including morphine from medicinal plants began at Merck in 1826.
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Kemp, DH, Stone BF and Binnington KC (1982) Tick Attachment and Feeding, in Current Themes in Tropical Science Vol 1, Physiology of Ticks, Obenchain FD and Galun R (eds); Pergamon Press, 1982. The host reacts against the tick lesion by haemostasis, inflammation and cell mediated immunity (CMI). An array of pharmacologically active substances is injected with the saliva of the tick, including anticoagulants, PGE2, prostacyclin, apyrase and in certain tick species antihistamines. PGE2 and prostacyclin inhibit platelet aggregation and dilate blood vessels.
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Lisdexamfetamine is an inactive prodrug that is converted in the body to dextroamphetamine, a pharmacologically active compound which is responsible for the drug's activity. After oral ingestion, lisdexamfetamine is broken down by enzymes in red blood cells to form L-lysine, a naturally occurring essential amino acid, and dextroamphetamine. The conversion of lisdexamfetamine to dextroamphetamine is not affected by gastrointestinal pH and is unlikely to be affected by alterations in normal gastrointestinal transit times. The optical isomers of amphetamine, i.e.
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Following oral administration, nitazoxanide is rapidly hydrolyzed to the pharmacologically active metabolite, tizoxanide, which is 99% protein bound. Tizoxanide is then glucuronide conjugated into the active metabolite, tizoxanide glucuronide. Peak plasma concentrations of the metabolites tizoxanide and tizoxanide glucuronide are observed 1–4 hours after oral administration of nitazoxanide, whereas nitazoxanide itself is not detected in blood plasma. Roughly of an oral dose of nitazoxanide is excreted as its metabolites in feces, while the remainder of the dose excreted in urine.
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M-1 and M-23 are, like cerivastatin, pharmacologically active, with comparable potencies. Combination of the latter leads to another minor metabolite, that is not detectable in plasma, which is also known as M-24. Following a 0.8 mg dose of cerivastatin, the mean steady state Cmax values for cerivastatin, M-1 and M-23 were 12.7, 0.55 and 1.4 μg/L, respectively. Hence, it can be concluded that the cholesterol-lowering effect is mostly due to the cerivastatin itself.
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On October 22, 2004, President Bush signed into law the Anabolic Steroid Control Act of 2004 (118 Stat. 1661). The bill was written to become effective in 90 days, which was January 20, 2005. This legislation places both AAS and some androgen prohormones on a list of controlled substances (a new type of "regulatory control"). Statutory definition of AAS: "The term 'anabolic steroid' means any drug or hormonal substance, chemically and pharmacologically related to testosterone (other than estrogens, progestins, corticosteroids and dehydroepiandrosterone)".
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Due to the esterases existing in the aqueous humour and ocular tissues, ibopamine can be rapidly hydrolysed to epinine which is the active molecule responsible for the mydriatic effect. The epinine, an analogue of dopamine, can stimulate dopamine receptors and to a lesser degree adrenergic receptors. Thus it is believed that epinine is the pharmacologically active moiety. It has been shown that the half-life of ibopamine is short to about 2 minutes in the aqueous humour owing to the fast hydrolysis.
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Sibutramine is well absorbed from the gastrointestinal tract (77%), but undergoes considerable first-pass metabolism, reducing its bioavailability. The drug itself reaches its peak plasma level after 1 hour and has also a half-life of 1 hour. Sibutramine is metabolized by cytochrome P450 isozyme CYP3A4 into two pharmacologically- active primary and secondary amines (called active metabolites 1 and 2) with half-lives of 14 and 16 hours, respectively. Peak plasma concentrations of active metabolites 1 and 2 are reached after three to four hours.
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99mTc-tetrofosmin (Myoview, GE healthcare), 99mTc-sestamibi (Cardiolite, Bristol-Myers Squibb now Lantheus Medical Imaging). Following this, the heart rate is raised to induce myocardial stress, either by exercise or pharmacologically with adenosine, dobutamine or dipyridamole (aminophylline can be used to reverse the effects of dipyridamole). SPECT imaging performed after stress reveals the distribution of the radiopharmaceutical, and therefore the relative blood flow to the different regions of the myocardium. Diagnosis is made by comparing stress images to a further set of images obtained at rest.
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It is said that Mering proposed this name because the most peaceful place he knew was the Italian city of Verona. It was not until the 1950s that the behavioural disturbances and physical dependence potential of barbiturates became recognized. Barbituric acid itself does not have any direct effect on the central nervous system and chemists have derived over 2,500 compounds from it that possess pharmacologically active qualities. The broad class of barbiturates is further broken down and classified according to speed of onset and duration of action.
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The burst suppression pattern varies with the brain anesthetic concentration when pharmacologically inducing coma. Level of suppression is adjustable by decreasing or increasing anesthetic infusion rate, thus adjusting the level of inactivation. While burst suppression has typically been viewed as a homogeneous brain state, recent studies have shown that bursts and suppressions can occur in specific regions while other regions are unaffected. The fact that the burst suppression pattern persists after a patient undergoes cortical deafferentation indicates that burst suppression represents an intrinsic dynamic mode of cortex.
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The rule is important to keep in mind during drug discovery when a pharmacologically active lead structure is optimized step- wise to increase the activity and selectivity of the compound as well as to ensure drug-like physicochemical properties are maintained as described by Lipinski's rule. Candidate drugs that conform to the RO5 tend to have lower attrition rates during clinical trials and hence have an increased chance of reaching the market. Omeprazole is a popular drug that conforms to Lipinski's rule of five.
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Recently, several small-molecule compounds have also been developed to target the same, highly positively charged area of the ARM domain (CGP049090, PKF118-310, PKF115-584 and ZTM000990). In addition, β-catenin levels can also be influenced by targeting upstream components of the Wnt pathway as well as the β-catenin destruction complex. The additional N-terminal binding pocket is also important for Wnt target gene activation (required for BCL9 recruitment). This site of the ARM domain can be pharmacologically targeted by carnosic acid, for example.
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By the early 1990s, after AAS were scheduled in the U.S., several pharmaceutical companies stopped manufacturing or marketing the products in the U.S., including Ciba, Searle, Syntex, and others. In the Controlled Substances Act, AAS are defined to be any drug or hormonal substance chemically and pharmacologically related to testosterone (other than estrogens, progestins, and corticosteroids) that promote muscle growth. The act was amended by the Anabolic Steroid Control Act of 2004, which added prohormones to the list of controlled substances, with effect from January 20, 2005.
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Apalutamide acts as a selective competitive silent antagonist of the androgen receptor (AR), via the ligand-binding domain, and hence is an antiandrogen. It is similar both structurally and pharmacologically to the second-generation NSAA enzalutamide, but shows some advantages, including higher antiandrogenic activity as well as several-fold reduced central nervous system distribution. The latter difference may reduce its comparative risk of seizures and other central side effects. Apalutamide has 5- to 10-fold greater affinity for the AR than bicalutamide, a first-generation NSAA.
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Unlike MDMA, MBDB is not internationally scheduled under the United Nations Convention on Psychotropic Substances. The thirty-second meeting of the WHO Expert Committee on Drug Dependence (September 2000) evaluated MBDB and recommended against scheduling. From the WHO Expert Committee assessment of MBDB: :Although MBDB is both structurally and pharmacologically similar to MDMA, the limited available data indicate that its stimulant and euphoriant effects are less pronounced than those of MDMA. There have been no reports of adverse or toxic effects of MBDB in humans.
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DNMT inhibitors have also been shown to increase levels of the reeling protein and GAD67 in cell cultures. Some of the current DNMT inhibitors, however, like zebularine and procainamide, do not cross the blood brain barrier and would not prove as effective a treatment. While DNMT inhibitors would prevent the addition of a methyl group, there is also research done on DNA demethylate inducers, which would pharmacologically induce the removal of methyl groups. Current antipsychotic drugs, like clozapine and sulpiride, have been shown to also induce demethylation.
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The pharmacologically active ingredient contained in bear bile is ursodeoxycholic acid (UDCA). This can be synthesized using cow or pig bile, or even using no animal ingredients. The generic drug name is Ursodiol and it is now being widely produced under brand names such as Actigall, Urso, Ursofalk, Ursogal and Ursotan. It was estimated in 2008 that 100,000 kg of synthetic UDCA was already being used each year in China, Japan and South Korea, and that the total world consumption may be double this figure.
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Normally, a pharmacologically inactive ingredient (excipient) termed a binder is added to help hold the tablet together and give it strength. A wide variety of binders may be used, some common ones including lactose, dibasic calcium phosphate, sucrose, corn (maize) starch, microcrystalline cellulose, povidone polyvinylpyrrolidone and modified cellulose (for example hydroxypropyl methylcellulose and hydroxyethylcellulose). Often, an ingredient is also needed to act as a disintegrant to aid tablet dispersion once swallowed, releasing the API for absorption. Some binders, such as starch and cellulose, are also excellent disintegrants.
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In 1983, Davis first advanced his hypothesis that tetrodotoxin (TTX) poisoning could explain the existence of Haitian zombies. This idea has been controversial and his 1985 follow-up book (The Serpent and the Rainbow) elaborating upon this claim has been criticized as containing a number of scientific inaccuracies. One of these is the suggestion that Haitian witchdoctors can keep "zombies" in a state of pharmacologically induced trance for many years. As part of his Haitian investigations, Davis commissioned the exhumation of a recently buried child.
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Using shRNA, they modelled Shank3, a synapse scaffolding protein known to be implicated in ASD phenotypes, insufficiency in the VTA of mice. They found that mice exhibited impaired social preferences and abnormal excitatory transmission which reduced the output of VTA DA neurons. Bellone and her team however, were able to modulate DA neuron activity both pharmacologically, by allosterically activating mGlur1s, and optogenetically, to enhance social preference and partially restore social behavior. In a recent collaboration with researchers at UNIL, Bellone explored neuroimmune and µ-opioid receptor-driven effects on sociability.
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Not all protein residues play equally important roles in allosteric regulation. The identification of residues that are essential to allostery (so-called “allosteric residues”) has been the focus of many studies, especially within the last decade. In part, this growing interest is a result of their general importance in protein science, but also because allosteric residues may be exploited in biomedical contexts. Pharmacologically important proteins with difficult-to-target sites may yield to approaches in which one alternatively targets easier-to-reach residues that are capable of allosterically regulating the primary site of interest.
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Thenoyltrifluoroacetone, C8H5F3O2S, is a chemical compound used pharmacologically as a chelating agent. It is an inhibitor of cellular respiration by blocking the respiratory chain at complex II. Perhaps the first report of TTFA as an inhibitor of respiration was by A. L. Tappel in 1960. Tappel had the (erroneous) idea that inhibitors like antimycin and alkyl hydroxyquinoline-N-oxide might work by chelating iron in the hydrophobic milieu of respiratory membrane proteins, so he tested a series of hydrophobic chelating agents. TTFA was a potent inhibitor, but not because of its chelating ability.
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Oxcarbazepine, for comparison, is also nearly completely absorbed from the gut, and peak plasma concentrations of licarbazepine are reached after 4.5 hours on average after oxcarbazepine intake. Plasma protein binding and half-life are of course the same. Other metabolites of ESL are the less active (R)-(−)-licarbazepine (5%; the stereoisomer of eslicarbazepine), the pharmacologically active oxcarbazepine (1%), and inactive glucuronides of all of these substances. The drug is excreted mainly via the urine, of which two thirds are in the form of eslicarbazepine and one third in the form of eslicarbazepine glucuronide.
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IST has been treated both pharmacologically and invasively, with varying degrees of success. IST, in and of itself, is not indicative of higher rates of mortality, and non-treatment is an option chosen by many if they have minimal symptoms. Some types of medication tried by cardiologists and other physicians include: beta blockers, selective sinus node If channel inhibitors (such as ivabradine), calcium channel blockers, and antiarrhythmic agents. Some SSRI drugs are also occasionally tried, as are treatments more commonly used to treat postural orthostatic tachycardia syndrome, such as fludrocortisone.
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The same act also introduced more stringent controls with higher criminal penalties for offenses involving the illegal distribution of anabolic steroids and human growth hormone. By the early 1990s, after non-medical use of anabolic steroids was criminalized in the U.S., several pharmaceutical companies stopped manufacturing or marketing the products. Some brand names included Ciba, Searle, and Syntex. In the Controlled Substances Act, anabolic steroids are defined to be any drug or hormonal substance chemically and pharmacologically related to testosterone (other than estrogens, progestins, and corticosteroids) that promote muscle growth.
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Pharmaceutical drugs are chemicals used for the alteration, diagnosis, prevention and treatment of disease, health conditions or structure/function of the human body. Some pharmaceutically active compounds (PhACs) can enter the environment by one route or another as the parent compound or as pharmacologically active metabolites. Drugs are developed with the intention of having a beneficial biological effect on the organism to which they are administered, but many such compounds all too often pass into the environment where they may exert an unwanted biological effect.Halling-Sorensen et al. 1998.
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In clinical trials, pherines formulated for intranasal administration in ultra low doses (nanogram to low microgram quantities) showed rapid onset of efficacy (10–15 minutes) and an excellent safety and tolerability profile. Pherines are also minimally invasive (do not require systemic absorption) to exert their pharmacological effects and can be used on demand Pherines described in the scientific literature include PH10, PH15, PH80, PH284 and PH94B (Aloradine, or 4,16-androstadien-3β-ol, a positional isomer of androstadienol). Pherines are chemically and pharmacologically different from natural pheromones including androstadienone, androstenone, androstenol, androsterone, and estratetraenol.
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Octreotide (brand name Sandostatin, Novartis Pharmaceuticals) is an octapeptide that mimics natural somatostatin pharmacologically, though is a more potent inhibitor of growth hormone, glucagon, and insulin than the natural hormone, and has a much longer half-life (about 90 minutes, compared to 2–3 minutes for somatostatin). Since it is absorbed poorly from the gut, it is administered parenterally (subcutaneously, intramuscularly, or intravenously). It is indicated for symptomatic treatment of carcinoid syndrome and acromegaly. It is also finding increased use in polycystic diseases of the liver and kidney.
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Barbituric acid is the parent compound of barbiturate drugs although barbituric acid itself is not pharmacologically active. Barbiturates were synthesized in 1864 by Adolf von Baeyer by combining urea and malonic acid (Figure 5). A synthesis process was later developed and perfected by French chemist Edouard Grimaux in 1879, making possible the subsequent widespread development of barbiturate derivatives. Malonic acid was later replaced by diethyl malonate, as using the ester avoids the need to deal with the acidity of the carboxylic acid and its unreactive carboxylate (see figure 6).
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This factor was named bradykinin potentiating factor, BPF. In 1968, with the collaboration of Dr. Lewis Joel Greene, from the Brookhaven National Laboratory, U.S., he isolated several pharmacologically active peptides responsible for the activity of BPF. Using those peptides, was demonstrated a general parallelism between bradykinin potentiation and inhibition of Angiotensin I conversion. Subsequently, his group elucidated the structure of the smallest peptide, and using the synthetic pentapeptide, demonstrated its ability to potentiate bradykinin and to inhibit the conversion of angiotensin I in vivo in experimental models of hypertension.
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Psilocin is the pharmacologically active agent in the body after ingestion of psilocybin or some species of psychedelic mushrooms. Psilocybin is rapidly dephosphorylated in the body to psilocin which acts as a 5-HT2A, 5-HT2C and 5-HT1A agonist or partial agonist. Psilocin exhibits functional selectivity in that it activates phospholipase A2 instead of activating phospholipase C as the endogenous ligand serotonin does. Psilocin is structurally similar to serotonin (5-HT), differing only by the hydroxyl group being on the 4-position rather than the 5 and the dimethyl groups on the nitrogen.
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Caroverine (Spasmium, Tinnitin, Tinnex) is a muscle-relaxing drug used in Austria and Switzerland to relieve spasms in smooth muscles (which include intestines, arteries, and other organs), and the use in those countries was extended to aid with cerebrovascular diseases there, and eventually to treat tinnitus. It is also used to treat tinnitus in India. Chemically, it is a quinoxalinedione and is available in both a base and hydrochloric acid forms. Pharmacologically, it has been described as a nonspecific calcium channel blocker and as an antagonist of both non-NMDA and NMDA glutamate receptors.
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PPARs were originally identified in Xenopus frogs as receptors that induce the proliferation of peroxisomes in cells. The first PPAR (PPARα) was discovered during the search of a molecular target for a group of agents then referred to as peroxisome proliferators, as they increased peroxisomal numbers in rodent liver tissue, apart from improving insulin sensitivity. These agents, pharmacologically related to the fibrates were discovered in the early 1980s. When it turned out that PPARs played a much more versatile role in biology, the agents were in turn termed PPAR ligands.
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After the attachment of the three phosphates gemcitabine is finally pharmacologically active as gemcitabine triphosphate (dFdCTP). After being thrice phosphorylated, gemcitabine can masquerade as deoxycytidine triphosphate and is incorporated into new DNA strands being synthesized as the cell replicates. When gemcitabine is incorporated into DNA it allows a native, or normal, nucleoside base to be added next to it. This leads to “masked chain termination” as gemcitabine is a “faulty” base, but due to its neighboring native nucleoside it eludes the cell's normal repair system (base-excision repair).
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The therapeutic pharmacological properties of zopiclone include hypnotic, anxiolytic, anticonvulsant, and myorelaxant properties. Zopiclone and benzodiazepines bind to the same sites on GABAA-containing receptors, causing an enhancement of the actions of GABA to produce the therapeutic and adverse effects of zopiclone. The metabolite of zopiclone called desmethylzopiclone is also pharmacologically active, although it has predominately anxiolytic properties. One study found some slight selectivity for zopiclone on α1 and α5 subunits, although it is regarded as being unselective in its binding to α1, α2, α3, and α5 GABAA benzodiazepine receptor complexes.
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In EEG studies, zopiclone significantly increases the energy of the beta frequency band and shows characteristics of high- voltage slow waves, desynchronization of hippocampal theta waves, and an increase in the energy of the delta frequency band. Zopiclone increases both stage 2 and slow-wave sleep (SWS), while zolpidem, an α1-selective compound, increases only SWS and causes no effect on stage 2 sleep. Zopiclone is less selective to the α1 site and has higher affinity to the α2 site than zaleplon. Zopiclone is therefore very similar pharmacologically to benzodiazepines.
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The Morris water maze task has been used to demonstrate the necessity of NMDA receptors in establishing spatial memories. In 1986, Richard Morris provided some of the first evidence that LTP was indeed required for the formation of memories in vivo. He tested the spatial memory of rats by pharmacologically modifying their hippocampus, a brain structure whose role in spatial learning is well established. Rats were trained on the Morris water maze, a spatial memory task in which rats swim in a pool of murky water until they locate the platform hidden beneath its surface.
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Intentionally consuming more than the recommended dosage of Delsym may result in euphoria, lack of coordination, hallucinations, apathy, feelings of dissociation, and disorientation. This is due to dextromethorphan as well as its pharmacologically-active metabolite dextrorphan, both dissociative drugs that work as NMDA receptor antagonists the same way nitrous oxide (N2O), ketamine, and phencyclidine (PCP) do. Because of the abuse potential, many pharmacies and large retail chains have begun taking precautions such as restricting sales to those under age 18 and limiting the number of sales of dextromethorphan-containing products per customer.
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Research chemicals are fundamental in the development of novel pharmacotherapies. Common medical laboratory uses include in vivo and animal testing to determine therapeutic value, toxicology testing by contract research organizations to determine drug safety, and analysis by drug test and forensic toxicology labs for the purposes of evaluating human exposure. Many pharmacologically active chemicals are sold online under the guise of "research chemicals," when in reality they are untested designer drugs that are being consumed by buyers taking advantage of many of the compounds' transitional or nonexistent legal status.
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To explore the underlying causes of post-stroke associated dementia, Buckwalter probed the B lymphocyte response to stroke that had been observed. She found that B lymphocytes infiltrate the brain and are found in neuropil and are associated with aberrant LTP and cognitive delays. Further, pharmacologically blocking B lymphocytes prevented cognitive delays after stroke. To look at the possibility of B cell mediated deficits in cognition in humans, Buckwalter and her colleagues measured autoantibodies in patients after stroke and found that increases in autoantibodies to myelin basic protein were associated with cognitive decline after stroke.
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With its three different reactive centers—nitrile, ester, acidic methylene site—ethyl cyanoacetate is a versatile synthetic building block for a variety of functional and pharmacologically active substances. It contains an acidic methylene group, flanked by both the nitrile and carbonyl, and so can be used in condensation reactions like the Knoevenagel condensation or the Michael addition. This reactivity is similar to that of esters of malonic acid. As an example of reactivity at the nitrile, diethyl malonate is obtained from cyanoacetic acid ethyl ester by reaction with ethanol in the presence of strong acids.
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With the isolation of cocaine in the mid-nineteenth century there began to be drugs available for local anesthesia. By the end of the nineteenth century the number of pharmacological options increased and they began to be applied both peripherally and neuraxially. Then in the twentieth century neuromuscular blockade allowed the anesthesiologist to completely paralyze the patient pharmacologically and breathe for him or her via mechanical ventilation. With these new tools the anesthetist could intensively manage the patient's physiology bringing about critical care medicine, which, in many countries, is intimately connected to anesthesiology.
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Fluperlapine (NB 106-689), also known as fluoroperlapine, is a morphanthridine (11H-dibenzo[b,e]azepine ) atypical antipsychotic with additional antidepressant and sedative effects. It was first synthesized in 1979, and then subsequently studied in animals and humans in 1984 and beyond, but despite demonstrating efficacy in the treatment of a variety of medical conditions including schizophrenia, psychosis associated with Parkinson's disease, depressive symptoms, and dystonia, it was never marketed. This was perhaps due to its capacity for producing potentially life-threatening agranulocytosis, similarly to clozapine, which it closely resembles both structurally and pharmacologically.
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Nordoxepin is pharmacologically active similarly to doxepin, but relative to doxepin, is much more potent and selective as a norepinephrine reuptake inhibitor. In general, the demethylated variants of tertiary amine TCAs like doxepin are much more potent inhibitors of norepinephrine reuptake, less potent inhibitors of serotonin reuptake, and less potent in their antiadrenergic, antihistamine, and anticholinergic activities. Nordoxepin is formed from doxepin mainly by CYP2C19 (>50% contribution), while CYP1A2 and CYP2C9 are involved to a lesser extent, and CYP2D6 and CYP3A4 are not involved. Hydroxylation of doxepin and nordoxepin is mediated mainly by CYP2D6.
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Intravaginal administration is a route of administration where the medication is inserted into the vagina as a creme or tablet. Pharmacologically, this has the potential advantage of promoting therapeutic effects primarily in the vagina or nearby structures (such as the vaginal portion of cervix) with limited systemic adverse effects compared to other routes of administration. Medications used to ripen the cervix and induce labor are commonly administered via this route, as are estrogens, contraceptive agents, propranolol, and antifungals. Vaginal rings can also be used to deliver medication, including birth control in contraceptive vaginal rings.
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Vandetanib is an inhibitor of vascular endothelial growth factor receptor-2, epidermal growth factor receptor, and RET tyrosine kinases. RET tyrosine kinases; it weakly inhibits VEGFR-3. Metabolites of vandetanib (top left): N-desmethylvandetanib (bottom left, via CYP3A4), vandetanib-N- oxide (bottom right, via FMO1 and FMO3), both pharmacologically active, and a minor amount of a glucuronide. Vandetanib is well absorbed from the gut, reaches peak blood plasma concentrations 4 to 10 hours after application, and has a half-life of 19 days on average, per pharmacokinetic studies.
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Amanita muscaria Muscarine, L-(+)-muscarine, or muscarin is a natural product found in certain mushrooms, particularly in Inocybe and Clitocybe species, such as the deadly C. dealbata. Mushrooms in the genera Entoloma and Mycena have also been found to contain levels of muscarine which can be dangerous if ingested. Muscarine has been found in harmless trace amounts in Boletus, Hygrocybe, Lactarius and Russula. Trace concentrations of muscarine are also found in Amanita muscaria, though the pharmacologically more relevant compound from this mushroom is the Z-drug-like alkaloid muscimol.
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Lorazepam is highly protein bound and is extensively metabolized into pharmacologically inactive metabolites. Due to its poor lipid solubility, lorazepam is absorbed relatively slowly by mouth and is unsuitable for rectal administration. However, its poor lipid solubility and high degree of protein binding (85–90%) mean its volume of distribution is mainly the vascular compartment, causing relatively prolonged peak effects. This contrasts with the highly lipid- soluble diazepam, which, although rapidly absorbed orally or rectally, soon redistributes from the serum to other parts of the body, in particular, body fat.
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Pharmacologically, bath salts usually contain a cathinone, typically methylenedioxypyrovalerone (MDPV), methylone or mephedrone; however, the chemical composition varies widely and products labeled with the same name may also contain derivatives of pyrovalerone or pipradrol. In Europe the main synthetic cathinone is mephedrone, whereas in the US MDPV is more common. Very little is known about how bath salts interact with the brain and how they are metabolized by the body. Scientists are inclined to believe that bath salts have a powerful addictive potential and can increase users' tolerance.
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Dr. Arntzen's research focus spans plant cell-molecular biology and protein engineering. He was an early proponent of using plant biotechnology to enhance food quality and value, to express pharmacologically active products in plants, and to overcome health and agricultural constraints in the developing world. He is a pioneer in the development of plant-based vaccines for human disease prevention with special emphasis on needs of poor countries and disease prevention in animal agriculture. After 2001, this research was extended to the creation of effective vaccines and therapeutics to reduce the threats of biowarfare agents.
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The following outline is provided as an overview of and topical guide to anesthesia: Anesthesia - pharmacologically induced and reversible state of amnesia, analgesia, loss of responsiveness, loss of skeletal muscle reflexes or decreased sympathetic nervous system, or all simultaneously. This allows patients to undergo surgery and other procedures without the distress and pain they would otherwise experience. An alternative definition is a "reversible lack of awareness," including a total lack of awareness (e.g. a general anesthetic) or a lack of awareness of a part of the body such as a spinal anesthetic.
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Turkey berry contains a number of potentially pharmacologically active chemicals including the sapogenin steroid chlorogenin.Badola and others 1993 Aqueous extracts of turkey berry are lethal to mice by depressing the number of erythrocytes, leukocytes and platelets in their blood (Tapia and others 1996). Extracts of the plant are reported to be useful in the treatment of hyperactivity,Null, 2001 colds and cough,CPR Environmental Education Centre, 2001 pimples, skin diseases, and leprosy.Liogier, 1990 Methyl caffeate, extracted from the fruit of S. torvum, shows an antidiabetic effect in streptozotocin-induced diabetic rats.
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The first recorded provings were published by Hahnemann in his 1796 Essay on a New Principle. His Fragmenta de Viribus (1805) contained the results of 27 provings, and his 1810 Materia Medica Pura contained 65. For James Tyler Kent's 1905 Lectures on Homoeopathic Materia Medica, 217 preparations underwent provings and newer substances are continually added to contemporary versions. Though the proving process has superficial similarities with clinical trials, it is fundamentally different in that the process is subjective, not blinded, and modern provings are unlikely to use pharmacologically active levels of the substance under proving.
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A biological target is anything within a living organism to which some other entity (like an endogenous ligand or a drug) is directed and/or binds, resulting in a change in its behavior or function. Examples of common classes of biological targets are proteins and nucleic acids. The definition is context-dependent, and can refer to the biological target of a pharmacologically active drug compound, the receptor target of a hormone (like insulin), or some other target of an external stimulus. Biological targets are most commonly proteins such as enzymes, ion channels, and receptors.
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Hoffmann was working at Bayer pharmaceutical company in Elberfeld, Germany, and his supervisor Heinrich Dreser instructed him to acetylate morphine with the objective of producing codeine, a constituent of the opium poppy that is pharmacologically similar to morphine but less potent and less addictive. Instead, the experiment produced an acetylated form of morphine one and a half to two times more potent than morphine itself. The head of Bayer's research department reputedly coined the drug's new name of "heroin," based on the German heroisch which means "heroic, strong" (from the ancient Greek word "heros, ήρως").
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Psilocybin is converted in the liver to the pharmacologically active psilocin, which is then either glucuronated to be excreted in the urine or further converted to various psilocin metabolites. Psilocybin is metabolized mostly in the liver. As it becomes converted to psilocin, it undergoes a first-pass effect, whereby its concentration is greatly reduced before it reaches the systemic circulation. Psilocin is broken down by the enzyme monoamine oxidase to produce several metabolites that can circulate in the blood plasma, including 4-hydroxyindole-3-acetaldehyde, 4-hydroxytryptophol, and 4-hydroxyindole-3-acetic acid.
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Psilocybin (O-phosphoryl-4-hydroxy-N,N-dimethyltryptamine, 4-PO-Psilocin, or 4-PO-HO-DMT) is a prodrug that is converted into the pharmacologically active compound psilocin in the body by a dephosphorylation reaction. This chemical reaction takes place under strongly acidic conditions, or under physiological conditions in the body, through the action of enzymes called alkaline phosphatases. Psilocybin is a tryptamine compound with a chemical structure containing an indole ring linked to an ethylamine substituent. It is chemically related to the amino acid tryptophan, and is structurally similar to the neurotransmitter serotonin.
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The scientists or doctors who oppose water fluoridation argue that it has no or little cariostatic benefits, may cause serious health problems, is not effective enough to justify the costs, and is pharmacologically obsolete. Arvid Carlsson has argued that fluoridation violates modern pharmacological principles and doesn't take into account individual variations in response, which can be considerable even when the dosage is fixed. Paul Connett has stated "It’s politics that is interfering with science in this issue...It’s a matter of political will, and you cannot change political will if you don’t get the people. We must involve the people.".
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MEAI (5-methoxy-2-aminoindane or 5-MeO-AI or Chaperon) is a recreational drug and binge drinking prevention drug, first chemically described in 1980, and first pharmacologically described in a peer reviewed paper in 2017 by David Nutt et al., followed by another in February 2018 which detailed pharmacokinetics, pharmacodynamics and metabolism of MEAI. In 2018, a company in the United States began offering an MEAI-based drink called "Pace". MEAI was an early candidate of alcohol replacement drugs that came to market during a late 2010s movement to replace alcohol with less-toxic alternatives spearheaded by British psychopharmacologist David Nutt.
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Biovista Inc.’s technology platform integrates literature-based discovery algorithms with Semantic search technologies to identify and rank potential solutions to a variety of drug development related problems such as predicting the adverse events of compounds, identifying suitable biomarkers for diseases and discovering new indications for existing drugs or drug combinations. Biovista’s correlation engine scans potential interactions between pharmacologically relevant entities resulting in a correlation database. The database itself is based on a proprietary design that combines the Relational database management system (RDBMS) model with the Object-Oriented model allowing researchers to obtain preliminary answers in weeks rather than years.
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These studies provide insight into the specific neurochemical mechanisms involved in the facilitation of BSR, and how reward perception can be modulated by pharmacologically altering the activity of specific neurotransmitter systems. Pharmacological manipulation of these systems can have either a direct or indirect effect on the activity of the reward circuitry. Understanding drug-specific effects on ICSS response thresholds has helped elucidate how different neurotransmitter systems influence the reward circuitry by either potentiating or suppressing sensitivity to rewarding stimulation and influencing motivation to perform reward-associated behaviors. BSR and drugs of addiction produce their rewarding effects through shared neuroanatomical and neurochemical mechanisms.
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Bonobos treat sexual activity as a very versatile form of social interaction, with purposes ranging from stress reduction to conflict resolution. Females tend to collectively dominate males by forming alliances and use sexuality to control males. Pathological overactivity of the dopaminergic mesolimbic pathway in the brain—forming either psychiatrically, during mania, or pharmacologically, as a side effect of dopamine agonists, specifically D3-preferring agonists—is associated with various addictions and has been shown to result among some subjects of either sex in overindulgent, sometimes hypersexual, behavior. Polyandrous mating is positively correlated with testicle-to-body weight across bushcricket taxa (see Sperm competition).
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The mould Penicillium chrysogenum was the source of penicillin G. Many species produce metabolites that are major sources of pharmacologically active drugs. Particularly important are the antibiotics, including the penicillins, a structurally related group of β-lactam antibiotics that are synthesized from small peptides. Although naturally occurring penicillins such as penicillin G (produced by Penicillium chrysogenum) have a relatively narrow spectrum of biological activity, a wide range of other penicillins can be produced by chemical modification of the natural penicillins. Modern penicillins are semisynthetic compounds, obtained initially from fermentation cultures, but then structurally altered for specific desirable properties.
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Bradykinin (Greek brady-, slow; -kinin, kīn(eîn) to move) is a peptide that promotes inflammation. It causes arterioles to dilate (enlarge) via the release of prostacyclin, nitric oxide, and endothelium-derived hyperpolarizing factor and makes veins constrict, via prostaglandin F2, thereby leading to leakage into capillary beds, due to the increased pressure in the capillaries. Bradykinin is a physiologically and pharmacologically active peptide of the kinin group of proteins, consisting of nine amino acids. A class of drugs called angiotensin converting enzyme inhibitors (ACE inhibitors) increase bradykinin levels by inhibiting its degradation, thereby increasing its blood pressure lowering effect.
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Mango, in moist Brazilian tropics Mango flowers in Sri Lanka Mangiferin (a pharmacologically active hydroxylated xanthone C-glycoside) is extracted from mango at high concentrations from the young leaves (172 g/kg), bark (107 g/kg), and from old leaves (94 g/kg). Allergenic urushiols are present in the fruit peel and can trigger contact dermatitis in sensitised individuals. This reaction is more likely to occur in people who have been exposed to other plants from the family Anacardiaceae, such as poison oak and poison ivy, which are widespread in the United States.Urushiol CASRN: 53237-59-5 TOXNET (Toxicology Data Network) NLM (NIH).
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Mantella baroni is a very active forager and can consume a greater number of prey (consisting of large arthropods) than any other Mantella species, consisting of large arthropods. While most frog species are nocturnal, the Mantella baroni is a diurnal hunter. Its diet consists mainly of ants, while also consuming a number of other types of arthropods like beetles, spiders, and mites. Ingesting mites allows them to secrete high pharmacologically-active alkaloid concentrations in their skin, making them toxic to predators, with their bright colors serving as a warning sign that ingestion could be dangerous and induce sickness.
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Single 20 to 40mg oral doses generally give rise to peak plasma esomeprazole concentrations of 0.5-1.0mg/l within 1–4 hours, but after several days of once-daily administration, these levels may increase by about 50%. A 30-minute intravenous infusion of a similar dose usually produces peak plasma levels on the order of 1–3mg/l. The drug is rapidly cleared from the body, largely by urinary excretion of pharmacologically inactive metabolites such as 5-hydroxymethylesomeprazole and 5-carboxyesomeprazole. Esomeprazole and its metabolites are analytically indistinguishable from omeprazole and the corresponding omeprazole metabolites unless chiral techniques are employed.
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Extracellular succinate can act as a signaling molecule with hormone-like function, targeting a variety of tissues such as blood cells, adipose tissue, immune cells, the liver, the heart, the retina and primarily the kidney. The G-protein coupled receptor, GPR91 also known as SUCNR1, serves as the detector of extracellular succinate. Arg99, His103, Arg252, and Arg281 near the center of the receptor generate a positively charged binding site for succinate. The ligand specificity of GPR91 was rigorously tested using 800 pharmacologically active compounds and 200 carboxylic acid and succinate-like compounds, all of which demonstrated significantly lower binding affinity.
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A variety of techniques can be used to generate the pictures of blood vessels, both arteries and veins, based on flow effects or on contrast (inherent or pharmacologically generated). The most frequently applied MRA methods involve the use intravenous contrast agents, particularly those containing gadolinium to shorten the T1 of blood to about 250 ms, shorter than the T1 of all other tissues (except fat). Short-TR sequences produce bright images of the blood. However, many other techniques for performing MRA exist, and can be classified into two general groups: 'flow-dependent' methods and 'flow-independent' methods.
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She proposed that a heat shock protein, hsp90, may act in the same way, normally preventing phenotypic consequences of genetic changes, but showing all changes at once when the HSP system is overloaded, either pharmacologically or under stressful environmental conditions. Susan Lindquist Most of these variations are likely to be harmful, but a few unusual combinations may produce valuable new traits, spurring the pace of evolution. Cancer cells too have an extraordinary ability to evolve. Lindquist's lab investigates closely related evolutionary mechanisms involved in the progression of cancerous tumors and in the evolution of antibiotic- resistant fungi.
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On January 15, 2007, Senators Dave Oehlke (R) and Randel Christmann (R), together with Representative Brenda Heller (R) proposed Senate Bill 2317 to classify Salvia divinorum as Schedule I controlled substance. The original text of the bill only mentioned Salvia divinorum. The Senate Judiciary Committee amended this on April 5, 2007, changing the bill wording to include salvinorin A and "any of the active ingredients" of Salvia divinorum. Daniel Siebert has questioned this vague wording – "since it could be interpreted to include many commonly occurring pharmacologically active compounds, such as tannins, oleanolic acid, ursolic acid, etc".
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Brivaracetam exhibits linear pharmacokinetics over a wide dose range, is rapidly and completely absorbed after oral administration, has an elimination half-life of seven to eight hours, and has plasma protein binding of less than 20%. It is extensively metabolized (>90%), primarily via hydrolysis of the acetamide group, and secondarily through hydroxylation mediated by the liver enzyme CYP2C19. The three major metabolites (hydroxy, acid, and hydroxyacid) are pharmacologically inactive. Brivaracetam is eliminated as urinary metabolites, with over 95% of a radioactive test dose recovered in the urine within 72 hours, including only 8.6% as unchanged brivaracetam.
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Miller first dissected the neural circuits that are activated during re-exposure to an environment previously associated with cocaine. Miller found that, during expression of drug induced place preference, the Basolateral Amygdala complex provides more excitatory drive to the Nucleus Accumbens Core than the Prelimbic cortex. In a first author paper in Neuron, Miller reported that inhibiting ERK kinase MEK prevents the activation of ERK in the Nucleus Accumbens Core and inhibits conditioned place preference. Her findings suggested that memories of drug-cue pairings can be pharmacologically or therapeutically ameliorated to potentially reduce relapse in drug abusers.
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PPAR Although used clinically since the 1930s, if not earlier, the mechanism of action of fibrates remained unelucidated until, in the 1990s, it was discovered that fibrates activate PPAR (peroxisome proliferator-activated receptors), especially PPARα. The PPARs are a class of intracellular receptors that modulate carbohydrate and fat metabolism and adipose tissue differentiation. Activating PPARs induces the transcription of a number of genes that facilitate lipid metabolism. Fibrates are structurally and pharmacologically related to the thiazolidinediones, a novel class of anti-diabetic drugs that also act on PPARs (more specifically PPARγ) Fibrates are a substrate of (metabolized by) CYP3A4.
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Most perceptions of heartbeat sensations usually occur during a time of homeostatic perturbation, such as when the state of the body changes from external or internal influences such as physical exertion or elevated arousal states (e.g., riding a roller coaster, watching a scary movie, public speaking anxiety, or having a panic attack). For this reason, cardiac interoception is also sometimes studied by inducing perturbations of bodily state. This can be done pharmacologically using adrenaline-like drugs, such as isoproterenol, which mimics activation of the sympathetic nervous system, resulting in increased heart rate and respiration rate, similar to the “fight-or-flight” response.
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The MAPEG family (Membrane-Associated Proteins in Eicosanoid and Glutathione metabolism) consists of six human proteins, two of which are involved in the production of leukotrienes and prostaglandin E, important mediators of inflammation. Other family members, demonstrating glutathione S-transferase and peroxidase activities, are involved in cellular defense against toxic, carcinogenic, and pharmacologically active electrophilic compounds. This gene encodes a protein that catalyzes the conjugation of glutathione to electrophiles and the reduction of lipid hydroperoxides. This protein is localized to the endoplasmic reticulum and outer mitochondrial membrane where it is thought to protect these membranes from oxidative stress.
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RASSLs and DREADDs are families of designer G-protein-coupled receptors (GPCRs) built specifically to allow for precise spatiotemporal control of GPCR signaling in vivo. These engineered GPCRs, called RASSLs (receptors activated solely by synthetic ligands), are unresponsive to endogenous ligands but can be activated by nanomolar concentrations of pharmacologically inert, drug-like small molecules. Currently, RASSLs exist for the interrogation of several GPCR signaling pathways, including those activated by Gs, Gi, Gq, Golf and β-arrestin. A major cause for success of RASSL resources has been open exchange of DNA constructs, and RASSL related resources.
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THC-O-phosphate is a water-soluble organophosphate ester derivative of tetrahydrocannabinol (THC), which functions as a metabolic prodrug for THC itself. It was invented in 1978 in an attempt to get around the poor water solubility of THC and make it easier to inject for the purposes of animal research into its pharmacology and mechanism of action. The main disadvantage of THC phosphate ester is the slow rate of hydrolysis of the ester link, resulting in delayed onset of action and lower potency than the parent drug. Pharmacologically, it parallels the action of psilocybin as a metabolic prodrug for psilocin.
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The physician William C. Cooper and the sinologist Nathan Sivin (1973) chose what the Chinese call rényào "human drugs" as a pilot experiment sample for pharmacologically analyzing the efficacy of drugs used in TCM. In contrast to many traditional Chinese plant, animal, and mineral pharmaceuticals with uncertain active constituents, the chemical composition of the human body and parts is well known, and "their therapeutic effectiveness, or lack of it, can be objectively, if approximately, estimated without reference to their Chinese context." (Cooper & Sivin 1973: 203). They selected 8 widely used human drugs from the 37 listed in Bencao gangmu chapter 52: human hair, nails, teeth, milk, blood, semen, saliva, and bone.
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Only 1% of the drug was eliminated in urine unchanged whereas 13% was eliminated as the major metabolite 2-oxo-3-hydroxy-LSD (O-H-LSD) within 24 hours. O-H-LSD is formed by cytochrome P450 enzymes, although the specific enzymes involved are unknown, and it does not appear to be known whether O-H-LSD is pharmacologically active or not. The oral bioavailability of LSD was crudely estimated as approximately 71% using previous data on intravenous administration of LSD. The sample was equally divided between male and female subjects and there were no significant sex differences observed in the pharmacokinetics of LSD.
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In October 2011, Murphy stated that the tumor had returned but that it was non-cancerous and that it was being treated pharmacologically. He is working on a tribute album to Death founder Chuck Schuldiner who died from pneumonia, caused by complications of his treatment for a brain tumor. He also produced Deron Miller's band World Under Blood. He also completed production of the industrial death metal band Dååth's second album, The Hinderers, which was released on Roadrunner Records, and Lazarus A.D.'s second album The Onslaught, and its follow-up Black Rivers Flow released on Metal Blade Records, and many other productions and mixes on various record labels.
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Residues from the breakdown of nitrofuran veterinary antibiotics, including nitrofurantoin, have been found in chicken in Vietnam, China, Brazil, and Thailand.FAO: Nitrofuran study The European Union banned the use of nitrofurans in food producing animals by classifying it in ANNEX IV (list of pharmacologically active substances for which no maximum residue limits can be fixed) of the Council Regulation 2377/90. The Food and Drug Administration (FDA) of the United States has prohibited furaltadone since February 1985 and withdrew the approval for the other nitrofuran drugs (except some topical uses) in January 1992. The topical use of furazolidone and nitrofurazone was prohibited in 2002.
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Ketamine may be quantitated in blood or plasma to confirm a diagnosis of poisoning in hospitalized patients, provide evidence in an impaired driving arrest or to assist in a medicolegal death investigation. Blood or plasma ketamine concentrations are usually in a range of 0.5–5.0 mg/L in persons receiving the drug therapeutically (during general anesthesia), 1–2 mg/L in those arrested for impaired driving and 3–20 mg/L in victims of acute fatal overdosage. Urine is often the preferred specimen for routine drug use monitoring purposes. The presence of norketamine, a pharmacologically-active metabolite, is useful for confirmation of ketamine ingestion.
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These invertebrates offer some advantages over vertebrates in animal testing, including their short life cycle and the ease with which large numbers may be housed and studied. However, the lack of an adaptive immune system and their simple organs prevent worms from being used in several aspects of medical research such as vaccine development. Similarly, the fruit fly immune system differs greatly from that of humans, and diseases in insects can be different from diseases in vertebrates; however, fruit flies and waxworms can be useful in studies to identify novel virulence factors or pharmacologically active compounds. Several invertebrate systems are considered acceptable alternatives to vertebrates in early-stage discovery screens.
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The mechanism for detecting reductions in PO2 has yet to be identified, there may be multiple mechanisms and could vary between species. Hypoxia detection has been shown to depend upon increased hydrogen sulfide generation produced by cystathionine gamma-lyase as hypoxia detection is reduced in mice in which this enzyme is knocked out or pharmacologically inhibited. The process of detection involves the interaction of cystathionine gamma-lyase with hemeoxygenase-2 and the production of carbon monoxide.Peng Y-J, Nanduri J, Raghuraman G, Souvannakitti D, Gadalla M.M, Kumar GK, Snyder SH, Prabhakar NR. (2010). H2S mediates O2 sensing in the carotid body PNAS 107 (23) 10719-10724.
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HMB is sold as an over-the-counter dietary supplement in the free acid form, β-hydroxy β-methylbutyric acid (HMB-FA), and as a monohydrated calcium salt of the conjugate base, calcium monohydrate (HMB-Ca, CaHMB). Since only a small fraction of HMB's metabolic precursor, , is metabolized into HMB, pharmacologically active concentrations of the compound in blood plasma and muscle can only be achieved by supplementing HMB directly. A healthy adult produces approximately 0.3 grams per day, while supplemental HMB is usually taken in doses of grams per day. HMB is sold at a cost of about per month when taken in doses of 3 grams per day.
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Inhibitory GABA, and excitatory glutamate, which regulate lateral septum (LS) activity, have been found to be increased during social play in juvenile rats. No sex differences were found in extracellular GABA concentrations during social playing, however, glutamate plays a major role in female social playing. When glutamate receptors are blocked in the LS pharmacologically, there is a significant decrease in female social playing, while males had no decrease in playing. This suggests that in the lateral septum, GABA neurotransmission is involved in social play behavior regulation in both sexes, while glutamate neurotransmission is sex-specific, involved in regulation of social play only in female juvenile rats.
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Though people may receive palliative care, pharmacologically decreasing a one's consciousness may be the only remaining option to help alleviate intolerable disease symptoms and suffering. Prior to receiving palliative sedation, persons should undergo careful consideration along with their health care team to make sure all other resources and treatment strategies have been exhausted. In the case the person is uncommunicable due to severe suffering, the individual's family member should be consulted as the decreasing the distress of family members is also key component and goal of palliative care and palliative sedation. The first step in consideration of palliative sedation is assessment of the person seeking the treatment.
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The material certainly is remarkably tough and has been used for plaiting into whip thongs. The Khoisan use of a decoction of some species for treating pain, plus the fact that many species of the Thymelaeaceae suggests that the material might be pharmacologically active, but there is no suggestion that the plants cause harm to stock. However, this harmlessness might well be for the same reason that the plants generally are of no value as forage for browsers, namely that they are unpalatable to stock.Watt, John Mitchell; Breyer-Brandwijk, Maria Gerdina: The Medicinal and Poisonous Plants of Southern and Eastern Africa 2nd ed Pub.
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Experimental studies have shown that general anaesthetics including ethanol are potent fluidizers of natural and artificial membranes. However, changes in membrane density and fluidity in the presence of clinical concentrations of general anaesthetics are so small that relatively small increases in temperature (~1 °C) can mimic them without causing anaesthesia. The change in body temperature of approximately 1 °C is within the physiological range and clearly it is not sufficient to induce loss of consciousness per se. Thus membranes are fluidized only by large quantities of anaesthetics, but there are no changes in membrane fluidity when concentrations of anaesthetics are small and restricted to pharmacologically relevant.
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The mechanism of action of itraconazole is the same as the other azole antifungals: it inhibits the fungal-mediated synthesis of ergosterol, via inhibition of lanosterol 14α-demethylase. Because of its ability to inhibit cytochrome P450 3A4 CC-3, caution should be used when considering interactions with other medications. Itraconazole is pharmacologically distinct from other azole antifungal agents in that it is the only inhibitor in this class that has been shown to inhibit both the hedgehog signaling pathway and angiogenesis. These distinct activities are unrelated to inhibition of the cytochrome P450 lanosterol 14 alpha-demethylase and the exact molecular targets responsible remain unidentified.
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It was rare for any patent medication to be pharmacologically effective, and none lived up to the miraculous promises made by their advertising. Patent medicine advertising was typically outlandish, eye-catching, and had little basis in reality. Advertisements emphasized exotic or scientific-sounding ingredients, featured endorsements from purported experts or celebrities, and often claimed that products were universal remedies or panaceas. Beginning in the early 20th century, the passage of consumer protection laws in countries like the United Kingdom, United States, and Canada began to regulate deceptive advertising and put limits on what ingredients could be used in medicines, putting an end to the dominance of patent medicines.
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Attempts to simulate this process pharmacologically have so far been unsuccessful. Techniques to manipulate the differentiation of "brown fat" could become a mechanism for weight loss therapy in the future, encouraging the growth of tissue with this specialized metabolism without inducing it in other organs. Until recently, brown adipose tissue was thought to be primarily limited to infants in humans, but new evidence has now overturned that belief. Metabolically active tissue with temperature responses similar to brown adipose was first reported in the neck and trunk of some human adults in 2007, and the presence of brown adipose in human adults was later verified histologically in the same anatomical regions.
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Ximelagatran was generally well tolerated in the trial populations, but a small proportion (5-6%) developed elevated liver enzyme levels, which prompted the FDA to reject an initial application for approval in 2004. The further development was discontinued in 2006 following reports of hepatotoxicity. Subsequent analysis of Phase 2 clinical study data using extreme value modelling (see Extreme value theory) showed that the elevated liver enzyme levels observed in Phase 3 clinical studies could have been predicted; if this had been known at the time, it might have affected decisions on future development of the compound. A chemically different but pharmacologically similar substance, AZD0837, was developed by Aztrazeneca for similar indications.
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Pathogenic overactivity of the dopaminergic mesolimbic pathway in the brain—forming either psychiatrically, during mania, or pharmacologically, as a side effect of dopamine agonists, specifically D3-preferring agonists—is associated with various addictions and has been shown to result among some in overindulgent, sometimes hypersexual, behavior. HPA axis dysregulation has been associated with hypersexual disorder. The American Association for Sex Addiction Therapy acknowledges biological factors as contributing causes of sex addiction. Other associated factors include psychological components (which affect mood and motivation as well as psychomotoric and cognitive functions), spiritual control, mood disorders, sexual trauma, and intimacy anorexia as causes or type of sex addiction.
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PAVA primarily affects the eyes, causing closure and severe pain. The pain to the eyes is reported to be greater than that caused by CS. The effectiveness rate is very high once PAVA gets into the eyes; however, there have been occasions where PAVA and CS have failed to work--especially when the subject is under the influence of alcohol or other drugs. Exposure to fresh moving air will normally result in a significant recovery from the effects of PAVA, within 15-35 minutes. Pharmacologically, like other capsaicinoids, PAVA works by direct binding to receptors (TRPV1) that normally produce the pain and sensation of heat, as if exposed to scalding heat.
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Erspamer was one of the first Italian pharmacologists to realize that fruitful scientific research benefits from building a relationship with the chemical and pharmaceutical industries. In the late 1950s, he established a collaboration with chemists at the Farmitalia company. The collaboration was useful, not only for the analysis of the structure of new molecules which he isolated and characterized pharmacologically, but also for the subsequent industrial synthesis of these chemicals and their synthetic analogs. Thanks to funding received from Farmitalia, over the years Erspamer collected more than five hundred species of marine organisms from all around the world, including amphibians, shellfish, sea anemones and other species.
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These colourations are often evidence that the specimen is, to a degree, toxic with pharmacologically active alkaloid secretions. There are of course, huge similarities between a few species of Mantella and Dendrobatidae when it comes to colouration, the most notable being between the Golden mantella (Mantella aurantiaca) and the Golden poison frog (Phyllobates terribilis) which clearly is reference to their uniform yellow colouration. Another example being between Cowan's mantella (Mantella cowanii) and certain variations of the Harlequin poison frog (Oophaga histrionica). The use of aposematism continues on to the ventral side of the specimens in most members of the genus, excluding the Golden mantella (Mantella aurantiaca) and Black-eared mantella (Mantella milotympanum).
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Outstanding among them became isoprenaline, N-isopropyl- noradrenaline, of Boehringer Ingelheim, studied pharmacologically along with adrenaline and other N-substituted noradrenaline derivatives by Richard Rössler (1897–1945) and Heribert Konzett (1912–2004) in Vienna. The Viennese pharmacologists used their own Konzett-Rössler test to examine bronchodilation. Intravenous injection of pilocarpine to induce bronchospasm was followed by intravenous injection of the agonists. “Arrangement of all amines according to their bronchodilator effect yields a series from the most potent, isopropyl-adrenaline, via the approximately equipotent bodies adrenaline, propyl-adrenaline and butyl-adrenaline, to the weakly active isobutyl-adrenaline.” Isoprenaline also exerted marked positive chronotropic and inotropic effects. Boehringer introduced it for use in asthma in 1940.
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Vitamin K is an essential factor to a hepatic gamma-glutamyl carboxylase that adds a carboxyl group to glutamic acid residues on factors II, VII, IX and X, as well as Protein S, Protein C and Protein Z. In adding the gamma-carboxyl group to glutamate residues on the immature clotting factors, Vitamin K is itself oxidized. Another enzyme, Vitamin K epoxide reductase (VKORC), reduces vitamin K back to its active form. Vitamin K epoxide reductase is pharmacologically important as a target of anticoagulant drugs warfarin and related coumarins such as acenocoumarol, phenprocoumon, and dicumarol. These drugs create a deficiency of reduced vitamin K by blocking VKORC, thereby inhibiting maturation of clotting factors.
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For example, teprotide, a peptide isolated from the venom of the Brazilian pit viper Bothrops jararaca, was a lead in the development of the antihypertensive agents cilazapril and captopril. Also, echistatin, a disintegrin from the venom of the saw-scaled viper Echis carinatus was a lead in the development of the antiplatelet drug tirofiban. In addition to the terrestrial animals and amphibians described above, many marine animals have been examined for pharmacologically active natural products, with corals, sponges, tunicates, sea snails, and bryozoans yielding chemicals with interesting analgesic, antiviral, and anticancer activities. Two examples developed for clinical use include ω-conotoxin (from the marine snail Conus magus) and ecteinascidin 743 (from the tunicate Ecteinascidia turbinata).
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Ivabradine Because of their relevance to generation of pacemaker activity and modulation of spontaneous frequency, f-channels are natural targets of drugs aimed to pharmacologically control heart rate. Several agents called "heart rate reducing agents" act by specifically inhibiting f-channel function. Ivabradine is the most specific and selective If inhibitor and the only member of this family that is now marketed for pharmacological treatment of chronic stable angina in patients with normal sinus rhythm who have a contraindication or intolerance to beta- blockers. Recent studies have also indicated that funny channel inhibition can be used to reduce the incidence of coronary artery disease outcomes in a subgroup of patients with heart rate ≥70 bpm.
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Further, the high standards applied to conventional medicines do not always apply to plant medicines, and dose can vary widely depending on the growth conditions of plants: older plants may be much more toxic than young ones, for instance. Pharmacologically active plant extracts can interact with conventional drugs, both because they may provide an increased dose of similar compounds, and because some phytochemicals interfere with the body's systems that metabolise drugs in the liver including the cytochrome P450 system, making the drugs last longer in the body and have a more powerful cumulative effect. Plant medicines can be dangerous during pregnancy. Since plants may contain many different substances, plant extracts may have complex effects on the human body.
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Lipinski's rule of five, also known as Pfizer's rule of five or simply the rule of five (RO5), is a rule of thumb to evaluate druglikeness or determine if a chemical compound with a certain pharmacological or biological activity has chemical properties and physical properties that would make it a likely orally active drug in humans. The rule was formulated by Christopher A. Lipinski in 1997, based on the observation that most orally administered drugs are relatively small and moderately lipophilic molecules. The rule describes molecular properties important for a drug's pharmacokinetics in the human body, including their absorption, distribution, metabolism, and excretion ("ADME"). However, the rule does not predict if a compound is pharmacologically active.
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After such repeated presentations of the CS and US, the CS will eventually elicit a blink before the US, a conditioned response or CR. Experiments showed that lesions localized either to a specific part of the interposed nucleus (one of the deep cerebellar nuclei) or to a few specific points in the cerebellar cortex would abolish learning of a conditionally timed blink response. If cerebellar outputs are pharmacologically inactivated while leaving the inputs and intracellular circuits intact, learning takes place even while the animal fails to show any response, whereas, if intracerebellar circuits are disrupted, no learning takes place—these facts taken together make a strong case that the learning, indeed, occurs inside the cerebellum.
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The rule regarding patients providing their own medications does not apply to the "drugs" oral glucose, activated charcoal, aspirin, or oxygen as the first two are not pharmacologically active; aspirin and oxygen have very few contraindications; they are not prescription controlled (except medical oxygen, which is not prescribed per patient, but rather per institution); and none are typically carried by patients. Thus, the OEC technician typically has access to these four interventions and may assist in their administration as warranted. Technicians must attend annual OEC refresher courses in order to maintain their certification. The OEC refreshers cover 1/3 of the OEC curriculum each year which cycles through the entire course every three years.
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Pharmacologically, it decreases the sympathetic stimulation on cardiac muscle predominantly through partial depletion of catecholamine via competitive inhibition of reuptake by storage granule, which lead to further depletion due to spontaneous leakage as a result of disturbance of equilibrium. This depletion mechanism is similar to reserpine because both agents target the same site on storage granule, however prenylamine shows a high affinity for cardiac tissue while reserpine is more selective toward brain tissue. Prenylamine also slows cardiac metabolism via calcium transport delay by blockade of magnesium-dependent calcium transport ATPase. It also demonstrate a beta blocker-like activity that result in reduction of heart rate however shows opposing effect on tracheal tissue response.
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Digitalis purpurea -- light purple A group of pharmacologically active compounds are extracted mostly from the leaves of the second year's growth, and in pure form are referred to by common chemical names, such as digitoxin or digoxin, or by brand names such as Crystodigin and Lanoxin, respectively. The two drugs differ in that digoxin has an additional hydroxyl group at the C-3 position on the B-ring (adjacent to the pentane). This results in digoxin having a half-life of about one day (and increasing with impaired kidney function), whereas digitoxin's is about 7 days and not affected by kidney function. Both molecules include a lactone and a triple- repeating sugar called a glycoside.
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Osan et al. (2002) found that in a network of theta neurons, there exist two different types of waves that propagate smoothly over the network, given a sufficiently large coupling strength. Such traveling waves are of interest because they are frequently observed in pharmacologically treated brain slices, but are hard to measure in intact animals brains. The authors used a network of theta models in favor of a network of leaky integrate-and-fire (LIF) models due to two primary advantages: first, the theta model is continuous, and second, the theta model retains information about "the delay between the crossing of the spiking threshold and the actual firing of an action potential".
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After discovering that the HVC is modulated according to behavioral state, Cardin then found that an upstream brain area, called the nucleus interfacialis (NiF) is also modulated by behavioral state. By pharmacologically inhibiting and exciting the NiF, Cardin found that the NiF is the primary integration site of behavioral state information and it relays this information to the HVC to drive its responsiveness to behavioral state. Following this study, Cardin showed that specifically the noradrenergic neurons in the NiF are what mediate NiF neuron responsiveness to brain state. Overall, Cardin's findings in graduate school highlight the noradrenergic neurons in the NiF as the critical integrators of brain state to relay state information during vocal learning in songbirds.
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Immunocontraception is one of the few alternatives to lethal methods for the direct control of wildlife populations. While there was research into the use of hormonal contraception for wildlife control as early as the 1950s that produced pharmacologically effective products, they all proved to be ineffective for wildlife control for a variety of practical reasons. Field trials of immunocontraception in wildlife, on the other hand, established that contraceptive vaccines could be delivered remotely by capture gun, were safe to use in pregnant animals, were reversible, and induced long-lasting infertility, overcoming these practical limitations. One concern about the use of hormonal contraceptives in general, but especially in wildlife, is that the sex steroid hormones that are used are easily passed from animal to animal.
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The IUPAC name of venlafaxine is 1-[2-(dimethylamino)-1-(4 methoxyphenyl)ethyl]cyclohexanol, though it is sometimes referred to as (±)-1-[a-[a-(dimethylamino)methyl]-p-methoxybenzyl]cyclohexanol. It consists of two enantiomers present in equal quantities (termed a racemic mixture), both of which have the empirical formula of C17H27NO2. It is usually sold as a mixture of the respective hydrochloride salts, (R/S)-1-[2-(dimethylamino)-1-(4 methoxyphenyl)ethyl]cyclohexanol hydrochloride, C17H28ClNO2, which is a white to off-white crystalline solid. Venlafaxine is structurally and pharmacologically related to the atypical opioid analgesic tramadol, and more distantly to the newly released opioid tapentadol, but not to any of the conventional antidepressant drugs, including tricyclic antidepressants, SSRIs, MAOIs, or RIMAs.
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The outputs of developmental bioelectric dynamics in vivo represent large-scale patterning decisions such as the number of heads in planaria, the shape of the face in frog development, and the size of tails in zebrafish. Experimental modulation of endogenous bioelectric prepatterns have enabled converting body regions (such as the gut) to a complete eye (Figure 9), inducing regeneration of appendages such as tadpole tails at non-regenerative contexts, and conversion of flatworm head shapes and contents to patterns appropriate to other species of flatworms, despite a normal genome. Recent work has shown the use of physiological modeling environments for identifying predictive interventions to target bioelectric states for repair of embryonic brain defects under a range of genetic and pharmacologically-induced teratologies.
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Botulinum toxin types A and B (Botox, Dysport, Xeomin, MyoBloc), used both medicinally and cosmetically, are natural products from the bacterium Clostridium botulinum. The serendipitous discovery and subsequent clinical success of penicillin prompted a large-scale search for other environmental microorganisms that might produce anti-infective natural products. Soil and water samples were collected from all over the world, leading to the discovery of streptomycin (derived from Streptomyces griseus), and the realization that bacteria, not just fungi, represent an important source of pharmacologically active natural products. This, in turn, led to the development of an impressive arsenal of antibacterial and antifungal agents including amphotericin B, chloramphenicol, daptomycin and tetracycline (from Streptomyces spp.), the polymyxins (from Paenibacillus polymyxa), and the rifamycins (from Amycolatopsis rifamycinica).
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Cocaine, the psychoactive constituent of coca The pharmacologically active ingredient of coca is the cocaine alkaloid, which is found in the amount of about 0.3 to 1.5%, averaging 0.8%, in fresh leaves. Besides cocaine, the coca leaf contains a number of other alkaloids, including methylecgonine cinnamate, benzoylecgonine, truxilline, hydroxytropacocaine, tropacocaine, ecgonine, cuscohygrine, dihydrocuscohygrine, nicotine, and hygrine. When chewed, coca acts as a mild stimulant and suppresses hunger, thirst, pain, and fatigue. Absorption of coca from the leaf is less rapid than nasal application of purified forms of the alkaloid (almost all of the coca alkaloid is absorbed within 20 minutes of nasal application, while it takes 2–12 hours after ingestion of the raw leaf for alkaline concentrations to peak.).
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Its vasodilatory effects are stipulated to be due to the stimulation of the production of nitric oxide in the vascular endothelium. It is hypothesized that meldonium may increase the formation of the gamma-butyrobetaine esters, potent parasympathomimetics and may activate the eNOS enzyme which causes nitric oxide production via stimulation of the M3 muscarinic acetylcholine receptor or specific gamma-butyrobetaine ester receptors. Meldonium is believed to continually train the heart pharmacologically, even without physical activity, inducing preparation of cellular metabolism and membrane structures (specifically in myocardial mitochondria) to survive ischemic stress conditions. This is done by adapting myocardial cells to lower fatty acid inflow and by activating glycolysis; the heart eventually begins using glycolysis instead of beta oxidation during real life ischaemic conditions.
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The longitudinal fissure plays a key role in corpus callosotomy, neurosurgery resulting in split brain, as it provides unobstructed access to the corpus callosum. Corpus callosotomy is one of the procedures used for pharmacologically treating intractable epilepsy cases, and it consists of the division of the nerve fibers running between the two hemispheres through the corpus callosum. A neurosurgeon separates the two hemispheres physically by pulling them apart with special tools, and cuts through either approximately two thirds of the fibers in the case of partial callosotomy, or the entirety in the case of complete callosotomy. Without the presence of longitudinal fissure, the corpus callosotomy procedure would be significantly more challenging and dangerous, as it would require the surgeon to navigate through densely connected cortical areas.
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In 1951 Isbell testified to Congress before the passage of the Boggs Act of 1952 that "smoking marijuana has no unpleasant aftereffects, no dependence is developed on the drug, and the practice can easily be stopped at any time." Isbell (1971b) (p 903) provides a liberal view of drug policy. He observes that the drug laws of the time are "excessively rigid and extremely punitive", and have not had any proven effect on the drug problem. He then states that "simple possession of a drug for one's own use should be a civil offense punishable only by a fine", and suggests the possibility that marijuana of low or moderate potency could be legalized and regulated like tobacco, while also observing that maintenance on barbiturates, cocaine, or amphetamine would not be "pharmacologically sound".
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Omega-3 fatty acids have been shown to disrupt inflammation cell signaling pathways by binding to the GPR120 receptor. This benefit however can be inhibited or even reversed if the ratio of Omega-6/Omega-3 is too high as Omega-6 serves as a precursor to inflammatory chemicals (prostaglandin and leukotriene eicosanoids) in the body. A high proportion of omega-6 to omega-3 fat in the diet shifts the physiological state in the tissues toward the pathogenesis of many diseases: prothrombotic, proinflammatory and proconstrictive. Omega-6 competes with Omega-3 for the same rate limiting factor which is required for the health-benefits of Omega-3, directly reducing the action of Omega-3 in addition to pharmacologically counteracting Omega-3 benefits through its own action as a pro-inflammatory agent.
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Integration of sensory, emotional, and cognitive information allows for these diverse functions of the IC, so Gogolla sought to understand how this integration occurs and how it is aberrantly functioning in ASD models, both idiopathic and monogenic. Through in vivo fluorescence imaging techniques, Gogolla was able to record from the IC and observe multisensory integration emerging in the IC throughout early development, but this process did not occur in ASD models. She further found that expression of inhibitory neuron markers was decreased compared to controls in the IC of ASD mouse models suggesting that inhibitory/excitatory circuit balance is disrupted. Following this result, they pharmacologically enhanced inhibitory signalling in juvenile mice via systemic injections of diazepam for two weeks and found that it rescued integration deficits in ASD models.
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Automation and low volume assay formats were leveraged by scientists at the NIH Chemical Genomics Center (NCGC) to develop quantitative HTS (qHTS), a paradigm to pharmacologically profile large chemical libraries through the generation of full concentration- response relationships for each compound. With accompanying curve fitting and cheminformatics software qHTS data yields half maximal effective concentration (EC50), maximal response, Hill coefficient (nH) for the entire library enabling the assessment of nascent structure activity relationships (SAR). In March 2010, research was published demonstrating an HTS process allowing 1,000 times faster screening (100 million reactions in 10 hours) at 1-millionth the cost (using 10−7 times the reagent volume) than conventional techniques using drop-based microfluidics. Drops of fluid separated by oil replace microplate wells and allow analysis and hit sorting while reagents are flowing through channels.
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The technique enables the mass creation and interrogation of libraries via affinity selection, typically on an immobilized protein target. A homogeneous method for screening DNA-encoded libraries has recently been developed which uses water-in-oil emulsion technology to isolate, count and identify individual ligand-target complexes in a single- tube approach. In contrast to conventional screening procedures such as high- throughput screening, biochemical assays are not required for binder identification, in principle allowing the isolation of binders to a wide range of proteins historically difficult to tackle with conventional screening technologies. So, in addition to the general discovery of target specific molecular compounds, the availability of binders to pharmacologically important, but so-far “undruggable” target proteins opens new possibilities to develop novel drugs for diseases that could not be treated so far.
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A picture of 150 mg tablets of the reversible MAOI drug moclobemide, brand name Aurorix. Moclobemide is a benzamide, derivative of morpholine, which acts pharmacologically as a selective, reversible inhibitor of monoamine oxidase-A (RIMA), a type of monoamine oxidase inhibitor (MAOI), and increases levels of norepinephrine (noradrenaline), dopamine, and especially serotonin in neuronal cells as well as in synaptic vesicles; extracellular levels also increase which results in increased monoamine receptor stimulation and suppression of REM sleep, down regulation of Beta-3 adrenergic receptors. A single 300 mg dose of moclobemide inhibits 80% of monoamine oxidase-A (MAO-A) and 30% of monoamine oxidase-B (MAO-B), blocking the decomposition of norepinephrine, serotonin and, to a lesser extent, dopamine. There is also some evidence of moclobemide possessing neuroprotective properties in rodent models.
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Secretion is stimulated by an antigen stimulus recognised by a pattern recognition receptor. IL-23 imbalance and increase is associated with autoimmune and cancerous diseases. It is thus a target for therapeutic research. IL-23 expressed by dendritic cells is further induced by thymic stromal lymphopoietin – a proallergic cytokine expressed by keratinocytes which is elevated in psoriatic lesions. So inhibition of this cytokine can be potential therapeutic option for patients with psoriasis by decreasing dendritic cells activation and thereby reduction of IL-23. Dermal dendritic cells are in contact with nociceptive neurons and if they are pharmacologically canceled there will be no dendritic cells to produce IL-23. If there is no IL-23 there will not be also inflammatory cells in the skin of psoriatic patients. IL-23 is also elevated during bacterial meningitis.
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In this study analgesia was produced in the periaqueductal gray matter, which is an area of the brain that is known to contain a large number of opiate binding sites. This study along with results from other studies conducted at the time suggested that there is a natural neural system in the brain, which uses a morphine-like substance to produce analgesia, however it was not known if the activation of this system was brought about pharmacologically by direct receptor stimulation or electrically by release of the endogenous substance. A combination of behavioral, pharmacological, and biochemical research led Akil and colleagues of the Barchas Laboratory at Stanford to the endorphins, specifically two peptides called enkephalins. What followed was a race against other research groups to isolate these morphine- like chemicals and determine what activates the system.
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Clairvius Narcisse (January 2, 1922 – 1994) was a Haitian man who claimed to have been turned into a zombie by a Haitian vodou, and forced to work as a slave. One hypothesis for Narcisse's account was that he had been administered a combination of psychoactive substances (oftentimes the paralyzing pufferfish venom tetrodotoxin and the strong deliriant Datura), which rendered him helpless and seemingly dead. The single greatest proponent of this possibility was Wade Davis, a graduate student in ethnobotany at Harvard University, who published two popular books based on his travels and ideas during and immediately following his graduate training. However, subsequent scientific examinations (using tools of analytical chemistry alongside critical review of earlier reports) have failed to support the presence of the claimed key pharmacologically active compounds in the supposed zombie preparation, which was central to the phenomena and mechanism reported by Davis.
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National laws include the British-era Indian Fisheries Act, 1897, which penalizes the killing of fish by poisoning water and by using explosives; the Environment Protection Act, 1986, being an umbrella act containing provisions for all environment related issues affecting fisheries and aquaculture industry in India, the Water (Prevention and Control of Pollution) Act, 1974 and the Wildlife Protection Act, 1972. The Wildlife Protection Act, 1972 prevents the fishing of rare species of fishes. In 1996, the Indian Supreme Court prohibited the setting up of Shrimp farm ponds except traditional and improved traditional types of ponds on the Coastal Regulation Zone and on the Chilka Lake and Pulicat Lake. The Order No 722 (E) of 2002 prohibited the use of certain antibiotics and pharmacologically active substances in hatcheries of production of the juveniles and larvae, or in manufacturing the fish feed or in processing fish products.
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Natural products chemistry is a distinct area of chemical research which was important in the history of chemistry, the sourcing of substances in early preclinical drug discovery research, the understanding of traditional medicine and ethnopharmacology, the evolution of technology associated with chemical separations, the development of modern methods in chemical structure determination by NMR and other techniques, and in identification of pharmacologically useful areas of chemical diversity space. In addition, natural products are prepared by organic synthesis, and have played a central role to the development of the field of organic chemistry by providing tremendously challenging targets and problems for synthetic strategy and tactics. In this regard, natural products play a central role in the training of new synthetic organic chemists, and are a principal motivation in the development of new variants of old chemical reactions (e.g., the Evans aldol reaction), as well as the discovery of completely new chemical reactions (e.g.
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It is important to distinguish between studies concerning synephrine as a single chemical entity (synephrine can exist in the form of either of two stereoisomers, d- and l-synephrine, which are chemically and pharmacologically distinct), and synephrine which is mixed with other drugs and/or botanical extracts in a "Supplement", as well as synephrine which is present as only one chemical component in a naturally-occurring mixture of phytochemicals such as the rind or fruit of a bitter orange. Mixtures containing synephrine as only one of their chemical components (regardless of whether these are of synthetic or natural origin) should not be assumed to produce exactly the same biological effects as synephrine alone. In physical appearance, synephrine is a colorless, crystalline solid and is water-soluble. Its molecular structure is based on a phenethylamine skeleton, and is related to those of many other drugs, and to the major neurotransmitters epinephrine and norepinephrine.
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While no binding sites have been identified and established unambiguously for ethanol at present, it appears that it affects ion channels, in particular ligand-gated ion channels, to mediate its effects in the central nervous system. Ethanol has specifically been found in functional assays to enhance or inhibit the activity of a variety of ion channels, including the GABAA receptor, the ionotropic glutamate AMPA, kainate, and NMDA receptors, the glycine receptor, the nicotinic acetylcholine receptors, the serotonin 5-HT3 receptor, voltage-gated calcium channels, and BK channels, among others. However, many of these actions have been found to occur only at very high concentrations that may not be pharmacologically significant at recreational doses of ethanol, and it is unclear how or to what extent each of the individual actions is involved in the effects of ethanol. In any case, ethanol has long shown a similarity in its effects to positive allosteric modulators of the GABAA receptor like benzodiazepines, barbiturates, and various general anesthetics.
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The Center for Advanced Study Marsilius Kolleg, situated in House Buhl, was founded in 2007 Among historical scientific achievements of Heidelberg researchers features prominently the invention of spectroscopy, and of the Bunsen burner; the discovery of chemical elements Caesium and Rubidium; the identification of the absolute point of ebullition; and the identification and isolation of nicotine as the main pharmacologically active component of tobacco. Modern scientific psychiatry; psychopharmacology; psychiatric genetics; environmental physics; and modern sociology were introduced as scientific disciplines by Heidelberg faculty. Almost 800 dwarf planets, the North America Nebula, and the return of Halley's Comet have been discovered and documented at institutes of the Heidelberg Center for Astronomy. Moreover, Heidelberg researchers invented the process of plastination to preserve body tissue, conducted the first successful transplantation of hematopoietic stem cells, and recently developed a new strategy for a vaccination against certain forms of cancer, which earned Harald zur Hausen of the university the Nobel Prize in Physiology or Medicine 2008.
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Smoking is a practice in which a substance is burned and the resulting smoke is breathed in to be tasted and absorbed into the bloodstream. Most commonly, the substance used is the dried leaves of the tobacco plant, which have been rolled into a small square of rice paper to create a small, round cylinder called a "cigarette". Smoking is primarily practised as a route of administration for recreational drug use because the combustion of the dried plant leaves vaporizes and delivers active substances into the lungs where they are rapidly absorbed into the bloodstream and reach bodily tissue. In the case of cigarette smoking these substances are contained in a mixture of aerosol particles and gases and include the pharmacologically active alkaloid nicotine; the vaporization creates heated aerosol and gas into a form that allows inhalation and deep penetration into the lungs where absorption into the bloodstream of the active substances occurs.
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Co- administration of quinidine, a potent CYP2D6 enzyme inhibitor, with tramadol, a combination which results in markedly reduced levels of desmetramadol, was found not to significantly affect the analgesic effects of tramadol in human volunteers. However, other studies have found that the analgesic effects of tramadol are significantly decreased or even absent in CYP2D6 poor metabolizers. The analgesic effects of tramadol are only partially reversed by naloxone in human volunteers, hence indicating that its opioid action is unlikely the sole factor; tramadol's analgesic effects are also partially reversed by α2-adrenergic receptor antagonists such as yohimbine, the 5-HT3 receptor antagonist ondansetron, and the 5-HT7 receptor antagonists SB-269970 and SB-258719. Pharmacologically, tramadol is similar to tapentadol and methadone in that it not only binds to the MOR, but also inhibits the reuptake of serotonin and norepinephrine due to its action on the noradrenergic and serotonergic systems, such as its "atypical" opioid activity. Tramadol has inhibitory actions on the 5-HT2C receptor.
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One of the most high-profile party pills products that Bowden developed was EASE. Bowden's organisation Stargate International began 'clinical trials' to distribute EASE, later identified as methylone, after receiving confirmation from the New Zealand Ministry of Health that the product was legal to import and sell. The initial advisement from the Ministry of Health stated: Methylone is structurally and pharmacologically similar in some respects to the illegal and neurotoxic drug of abuse MDMA, although its structure falls outside the definition of "Amphetamine analogues" as defined in Part 7 of Schedule C of New Zealand’s Misuse of Drugs Act. Following the screening of a locally produced documentary into EASE entitled The Truth Files, Associate Health Minister Jim Anderton released a statement classifying EASE as an illegal product, and provided the following assessment: Yesterday, Associate Health Minister Jim Anderton said advice from the chair of the Expert Advisory Committee on Drugs, Dr Ashley Bloomfield, showed Ease contained a substance called methylone, an "analogue" – similar to – cathinone, which is a Class B amphetamine controlled under the Misuse of Drugs Act.
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COMMITTEE FOR MEDICINAL PRODUCTS FOR HUMAN USEm SUMMARY OF POSITIVE OPINION for LUNIVIA – European Medicines Agency/Committee for Medicinal Products for Human Use, 23 Oct 2010 However, Sepracor withdrew its authorization application in 2009 after the EMA stated it would not be granting eszopiclone 'new active substance' status, as it was essentially pharmacologically and therapeutically too similar to zopiclone to be considered a new patentable product.Sepracor Pharmaceuticals Ltd withdraws its marketing authorisation application for Lunivia (eszopiclone) – European Medicines Agency, 15 May 2009 Since the patent on zopiclone has expired, this ruling would have allowed rival companies to also legally produce cheaper generic versions of eszopiclone for the European market.Data exclusivity and definition of a new active substance: suspension of generic escitalopram- containing medicines by CHMP – Bird and Bird Commercial Law 23 Apr 2010 , Sepracor has not resubmitted its authorization application and eszopiclone is not available in Europe. The deal with GSK fell through, and GSK instead launched a $3.3 billion deal to market Actelion's almorexant sleeping tablet, which entered phase 3 medical trials before development was abandoned due to side effects.
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4-Formylphenylboronic acid is used in Suzuki couplings, for example in the build up of pharmacologically active biphenyl compounds such as a precursor of the antihypertensive AT1 antagonist telmisartan in an improved synthesis: Synthese eines Telmisartan-Vorstufe durch Suzuki-Kupplung mit 4-FPBA Also palladium-catalyzed aryl heteroaryl linkages after Suzuki use 4-formylphenylboronic acid as a molecular building block, as for instance in the synthesis of aryl-benzimidazole derivatives (which bind to peroxisome- proliferator-activated receptors (PPARγ) and activate the expression of a variety of genes): Aryl-Heteroarylkupplung In a copper-mediated fluoroalkylation reaction, the boronic acid group of the 4-FPBA can be replaced with perfluorinated alkyl iodides (Rf-I) by a perfluoroalkyl chain under mild conditions. Umsetzung von 4-FPBA mit Perfluoralkyliodiden 4-Formyphenylboronic acid is used industrially as an enzyme stabilizer for proteases and in particular for lipases in liquid detergent preparations. The addition of 4-FPBA in amounts < 0.08 wt% in the formulation reduces the loss of hydrolytic activity of the enzymes used and increases the storage stability of enzyme-containing liquid detergents.
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