To put people on base and give a free base, that was tough, physically and mentally.
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Spiked seltzers like White Claw boast a gluten-free base and accessible flavor for beginning drinkers.
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It's Lofty305, Ruben Slikk, Postranaught and Free Base aka Posh God and that's all the homies in Metro Zu. Let's get into "Ultimate" now.
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However, if you cancel your Pro sub and revert back to Stadia's free Base tier, you'll lose access to those games until you re-subscribe.
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It remains unclear when Stadia will support Apple devices, or when voice chat is coming, or when the free "base" version of the service will launch.
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Google will be offering a free base subscription next year that lets gamers who purchase titles from the Stadia store stream them for free at 1080p 60fps.
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Big Tobacco research from the 1970s reports that nicotine salts are less harsh to inhale than the free-base nicotine in cigars and many other e-cig brands.
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But once again, he lacked command on his out pitch, the splitter, and was uncharacteristically wild, allowing the Orioles six free base runners: four on walks and two on hit batters.
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Although Wavebox costs $20 a year to unlock some of its better features, it works well enough in its free, base version, and it has powerful notification and menu bar controls.
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To find pitchers who approach Kershaw's walk numbers, you have to go back to the dawn of baseball, when it took nine balls, not four, before a batter got a free base.
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For a fraction of what we're paying now, we could provide a free base of primary care with mental-health and dental care as part of a large-scale build-out of C.H.C.s.
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And Pineda might not have left while trailing by a run had the Yankees' offense not repeatedly failed to capitalize on the free base runners being given out by Angels starter Parker Bridwell.
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The subscription is only available for GameStop Power-Up Rewards members, but that's not much of a stumbling block: While there are paid tiers that offer additional benefits, there's also a free base tier.
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If an actual Burner needed to inquire about a real issue, it'd instantly be buried below a pile of polls about free-base Bubba Gump shrimp and invites to R. Kelly's gluten-free sauna.
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They found that the Juul vape juices contained more nicotine and less of that harsh free-base than the other brands, according to a paper published in the journal Chemical Research in Toxicology in May.
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Though Google Stadia will arrive on November 19, that's more of a soft launch — You'll have to pay to get access for the first few months, and the free "base" tier doesn't arrive until February 2020.
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Nicotine salts form in the heat-dried tobacco leaves that are rolled into most cigarettes, and they're said to be easier to inhale than the free-base form of nicotine found in cigars, pipe tobacco, and many other vapes.
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Notable features are still missing from the service — like the ability to play Stadia on the vast majority of smartphones, including Apple devices and non-Google Android smartphones — but establishing the free "base" tier is an important step for Google's fledgling service.
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And despite the hitting of Ronald Torreyes, who accounted for all of the Yankees' offense with a two-run home run in the second and a double in the fourth, the Yankees — who had only four hits — were unable to capitalize on eight free base runners (seven walks and a hit batter).
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At launch in November (which will only be for Stadia Pro subscribers, the free Base tier won't be available until sometime in early 2020), Doronichev said Stadia will include all of the service's basic functionality like the ability to play across multiple devices, no need to install games or patches manually, built-in social features (making parties, managing your friends list, using voice chat) and of course, Stadia's game store.
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The salts in use are the free base hexahydrate (free base conversion ratio 0.715), and hydrochloride (0.833).
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The drug is used commercially mostly as the hydrochloride salt; the free base form is used rarely. The CAS Registry Number of the free base is 72-69-5 and of the hydrochloride is 894-71-3.
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The substance was sold both as a free base and as salt (hydrochloride).
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The free base can be obtained as an oil by treatment of the hydrochloride with base. It co-crystallizes with one molecule of ether as white silky needles, (m.p. 24–25 °C) upon cooling ethereal solutions. The free base melts at 39 °C.
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For example, compare the free base hydroxylamine (NH2OH) with the salt hydroxylamine hydrochloride (NH3OH+ Cl−).
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The chemical name of doxepin is (E/Z)-3-(dibenzo[b,e]oxepin-11(6H)-ylidene)-N,N-dimethylpropan-1-amine and its free base form has a chemical formula of C19H21NO with a molecular weight of 279.376 g/mol. The drug is used commercially almost exclusively as the hydrochloride salt; the free base has been used rarely. The CAS Registry Number of the free base is 1668-19-5 and of the hydrochloride is 1229-29-4.
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Butane torches are sometimes used in vaporizing cocaine free base (crack), methamphetamine or hash oil for inhalation.
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The salts in use are the citrate (free base conversion ratio 0.589), hydrobromide (0.773), and hydrochloride (0.883).
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Boron porphyrin compounds can be synthesized either from the free base porphyrin or from a lithium porphyrin starting material. Two representative examples are shown here. The first is the porphyrin free base reacted with BX3 in the presence of water. The second is Li2(ttp) reacted with BX3.
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Free base (freebase, free-base) is the conjugate base (deprotonated) form of an amine, as opposed to its conjugate acid (protonated) form. The amine is often an alkaloid, such as nicotine, cocaine, morphine, and ephedrine, or derivatives thereof. Freebasing is a more efficient method of self- administering alkaloids via the smoking route.
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The CAS Registry Number of the free base is 739-71-9 and of the maleate is 521-78-8.
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The drug is used commercially mostly as the hydrochloride salt; the free base form is used rarely and the embonate (pamoate) salt is used for intramuscular administration. The CAS Registry Number of the free base is 50-48-6, of the hydrochloride is 549-18-8, and of the embonate is 17086-03-2.
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Other tertiary amine TCAs include amitriptyline, imipramine, dosulepin (dothiepin), doxepin, and trimipramine. The chemical name of clomipramine is 3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-N,N-dimethylpropan-1-amine and its free base form has a chemical formula of C19H23ClN2 with a molecular weight of 314.857 g/mol. The drug is used commercially almost exclusively as the hydrochloride salt; the free base has been used rarely. The CAS Registry Number of the free base is 303-49-1 and of the hydrochloride is 17321-77-6.
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Triazane is an inorganic compound with the chemical formula or .IUPAC Goldbook Triazane is the third simplest acyclic azane after ammonia and hydrazine. It can be synthesized from hydrazine but is unstable and cannot be isolated in the free base form, only as salt forms such as triazanium sulfate. Attempts to convert triazanium salts to the free base release only diazene and ammonia.
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The wall cloud forms near the downdraft/updraft interface. This "interface" is the area between the precipitation area and the precipitation-free base. Wall clouds form when rain-cooled air from the downdraft is pulled into the updraft. This wet, cold air quickly saturates as it is lifted by the updraft, forming a cloud that seems to "descend" from the precipitation-free base.
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The drug is used commercially mostly as the hydrochloride salt; the dibudinate salt is or has been used for intramuscular injection in Argentina (brand name Nebril) and the free base form is not used. The CAS Registry Number of the free base is 50-47-5, of the hydrochloride is 58-28-6, and of the dibudinate is 62265-06-9.
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Ciprofloxacin immediate-release tablets contain ciprofloxacin as the hydrochloride salt, and the XR tablets contain a mixture of the hydrochloride salt as the free base.
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This page provides supplementary chemical data on Cocaine in free base form. More commonly available "powder cocaine" is a hydrochloride salt whose properties will differ.
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Higher doses produced effects that were described as psychedelic, such as "swirling, colored patterns typical of tryptamines, tending toward the arabesque". Free base bufotenin taken sublingually was found to be identical to intranasal use. The potency, duration, and psychedelic action was the same. Ott found vaporized free base bufotenin active from 2–8 mg with 8 mg producing "ring- like, swirling, colored patterns with eyes closed".
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However, since blood is buffered with carbonate at physiological pH (near 7.4), free-base amines will be rapidly converted back into their acid form. In fact, 94.19% of cocaine will exist as the acid form under equilibrium at pH=7.4, calculated using the Henderson- Hasselbalch equation assuming a pKa of 8.61. A small portion (5.81%) of cocaine will remain as free-base and pass through the blood-brain barrier; according to Le Chatelier's principle the acid form of cocaine will be continually converted to free-base as the base form is continually removed across the blood-brain barrier. Extraction kits for converting the hydrochloride to the base are commercially available.
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There are other cases when the use of copper should be avoided, such as coupling reactions involving substrates which potential copper ligands, for instance free-base porphyrins.
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Tolerance to benzodiazepines or alcohol will also reduce effects. Ethaqualone can be present as a free base, insoluble in water but soluble in alcohol and nonpolar solvents, or as a water-soluble hydrochloride salt which is about 85% as potent as the freebase by weight. The most common route of administration of etaqualone is oral, but snorting the salt or smoking the free base have also been reported.
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Free-base nicotine found in e-cigarette juice and tobacco cigarettes often stick to the respiratory tract whereas nicotine salts are unlikely to, giving them the higher percentage of nicotine delivery.
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A rain-free base with a wall cloud lowering in the foreground and precipitation in the background. Taken in Miami, Texas. A wall cloud (murus or pedestal cloud) is a large, localized, persistent, and often abrupt lowering of cloud that develops beneath the surrounding base of a cumulonimbus cloud and from which tornadoes sometimes form. It is typically beneath the rain-free base (RFB) portion of a thunderstorm, and indicates the area of the strongest updraft within a storm.
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Dosulepin exhibits (E) and (Z) stereoisomerism like doxepin but in contrast the pure E or trans isomer is used medicinally. The drug is used commercially as the hydrochloride salt; the free base is not used.
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178 °C; [α] = +42.0°, c 0.1 (H2O); (R)-(−)-C9H13NO2.HCl: m.p. 176 °C; [α] = −39.0°, c 0.2 (H2O) (−)-Synephrine, as the free base isolated from a Citrus source, has m.p. 162–164 °C (with decomposition).
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Mass Spectrometer Analysis: 2C-E 2,5-Dimethoxy-4-ethylphenethylamine is a colorless oil. Crystalline forms are obtained as the amine salt by reacting the free base with a mineral acid, typically hydrochloric acid (HCl). Shulgin does not report an exact boiling point for the free base, stating only that during one synthesis the fraction boiling between 90 and 100 °C at 0.25 mmHg pressure was collected and converted to the hydrochloride salt. Shulgin reports the melting point of the hydrochloride salt as 208.5–210.5 °C.
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Methaqualone peaks in the bloodstream within several hours, with a half-life of 20–60 hours. While the salt methaqualone hydrochloride is typically used clinically, methaqualone free-base was also marketed, namely as the methaqualone component of Mandrax, a combination drug which contained 250mg methaqualone and 25mg diphenhydramine within the same tablet. Oral dosage forms of methaqualone hydrochloride were manufactured as capsules, whereas oral dosage forms of methaqualone free-base were manufactured as tablets. Regular users build up a physical tolerance, requiring larger doses for the same effect.
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The free base is also active when smoked in a dose range of 5–20 mg. Smoking 4-acetoxy-DET greatly speeds up the onset; peak effects are experienced within 10 minutes, and are usually over within 1 hour.
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Etafedrine (INN) or ethylephedrine is a long-acting bronchodilator and has the brand name Nethaprin. It was previously commercially available as both the free base and as the hydrochloride salt from Sanofi-Aventis (now Sanofi) but is now no longer marketed.
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Myrophine is almost invariably used as the hydrochloride (free base conversion ratio 0.94) and has a DEA Administrative Controlled Substance Control Number of 9308. Myrophine is a Class A controlled substance in the UK, and is on the UN's Yellow list.
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The seven-spot ladybird synthesizes the toxic alkaloids, N-oxide coccinelline and its free base precoccinelline; depending on sex and diet, the spot size and coloration can provide some indication of how toxic the individual insect is to potential predators.
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This process is frequently done with baking soda (sodium bicarbonate), water, and a spoon. Once mixed and heated, the bicarbonate reacts with the hydrochloride of the powder cocaine, forming free base cocaine and carbonic acid (H2CO3) in a reversible acid-base reaction.
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WooCommerce is an open-source e-commerce plugin for WordPress. It is designed for small to large-sized online merchants using WordPress. Launched on September 27, 2011, the plugin quickly became popular for its simplicity to install and customize and free base product.
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The salts in use are the hydrobromide (HBr, free base conversion ratio 0.793), hydrochloride (HCl, 0.894), and HCl monohydrate (0.850). Isomethadone is also regulated internationally as a Schedule I controlled substance under the United Nations Single Convention on Narcotic Drugs of 1961.
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Nafarelin is a GnRH analogue, or a synthetic analogue of GnRH. It is a decapeptide and is also known as [6-D-(2-naphthyl)alanine]-GnRH. Nafarelin is marketed for medical use in both its free base (nafarelin) and acetate salt (nafarelin acetate) forms.
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Azo N-coupling In alkaline media, diazonium salt can react with most primary and secondary amines that exist as a free base and produce triazene. This chemical reaction is called azo N-coupling or the synthesis of azoamines. Synthesis of C.I. Pigment Yellow 12, a diarylide pigment.
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A selection of products containing BZP. BZP is a piperazine derivative which comes as either the hydrochloride salt or a free base. The hydrochloride salt is a white solid while the base form is a slightly yellowish-green liquid. BZP base is corrosive and causes burns.
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Some alkaloids are more stable as ionic salts than as free base. The salts usually exhibit greater water solubility. Common counterions include chloride, bromide, sulfate, phosphate, nitrate, acetate, oxalate, citrate, and tartrate. Ammonium salts formed from the acid-base reaction with hydrochloric acid are known as hydrochlorides.
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Amitriptyline is a highly lipophilic molecule having an octanol-water partition coefficient (pH 7.4) of 3.0,The Pharmaceutical Codex. 1994. Principles and practice of pharmaceutics, 12th edn. Pharmaceutical press while the log P of the free base was reported as 4.92.Hansch C, Leo A, Hoekman D. 1995.
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Veratridine has a pKa of 9.54. It is slightly soluble in ether, soluble in ethanol and DMSO, and freely soluble in chloroform. Solubility in water is pH-dependent; the free base form is slightly soluble, but easily dissolves in 1 M HCl. Its nitrate salt is slightly soluble in water.
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A pKa does not seem to have been recorded for MLA, but it is considered to be a weak base because it can be readily extracted into diethyl ether from an aqueous solution at pH 7.5-8. The optical rotation of the free base, [α]D was found to be +49° in alcohol.
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Pentoxyverine dihydrogen citrate, the salt that is commonly used for oral preparations, is a white to off-white, crystalline powder. It dissolves easily in water or chloroform, but not in benzene, diethyl ether, or petroleum ether. It melts at . Other orally available salts are the hydrochloride and the tannate; suppositories contain the free base.
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Buserelin is a GnRH analogue, or a synthetic analogue of GnRH. It is a nonapeptide and is also known as [D-Ser(tBu)6,des-Gly-NH210]GnRH ethylamide or as D-Ser(tBu)6EA10-GnRH. Buserelin is marketed for medical use in both its free base (buserelin) and acetate salt (buserelin acetate) forms.
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The Verge Retrieved on 12 May 2019. Each milliliter of a pod that uses nicotine of 5% is equivalent to nicotine found in 20 traditional cigarettes. Nicotine salts are created with free base nicotine and benzoic acid to produce an ionized(+) solution that is less volatile- smaller clouds- and less harsh, often described as smooth in anecdotal research.
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Atropine for comparison Like other anticholinergics, solifenacin is an ester of a carboxylic acid containing (at least) an aromatic ring with an alcohol containing a nitrogen atom. While in the prototype anticholinergic atropine the bicyclic ring is tropane, solifenacin replaces it with quinuclidine. The free base is a yellow oil, while the salt solifenacin succinate forms yellowish crystals.
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As a base, it is generally protonated in acidic environments (in an acid-base reaction). The protonated form is highly water- soluble and relatively stable, but can become oxidized if exposed to oxygen or other oxidants. In basic environments, dopamine is not protonated. In this free base form, it is less water-soluble and also more highly reactive.
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He noted that the visual effects of insufflated bufotenin were verified by one colleague, and those of vaporized bufotenin by several volunteers. Ott concluded that free base bufotenin taken intranasally and sublingually produced effects similar to those of Yopo without the toxic peripheral symptoms, such as facial flushing, observed in other studies in which the drug was administered intravenously.
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In the United States, MPPP is now in Schedule I of the Controlled Substances Act with a zero aggregate manufacturing quota as of 2014. The free base conversion ratio for salts includes 0.87 for the hydrochloride. It is listed under the Single Convention on Narcotic Drugs and is controlled in most countries in the same fashion as is morphine.
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The filtrate can then made basic with NH4OH and extracted with diethyl ether. Shaking the extract with 5% sodium hydroxide and retaining the organic layer removes the phenolic content of the extract. The hydrogen chloride salt is then obtained by mixing with hydrochloric acid and recrystallized from diethyl ether. The free base can then be obtained.
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Hydromorphinol (RAM-320, 14-Hydroxydihydromorphine), also is an opiate analogue that is a derivative of morphine, where the 14-position has been hydroxylated and the 7,8- double bond saturated. It has similar effects to morphine such as sedation, analgesia and respiratory depression, but is twice as potent as morphine and has a steeper dose-response curve and longer half- life. It is used in medicine as the bitartrate salt (free base conversion ratio 0.643, molecular weight 471.5) and hydrochloride (free base conversion ratio 0.770, molecular weight 393.9) It is also called α-Oxymorphol, and oxymorphol is itself a mixture of hydromorphinol and 4,5α-Epoxy-17-methylmorphinan-3,6β,14-triol, β-Oxymorphol, which is different at position 6 on the morphine carbon skeleton. Hydromorphinol was developed in Austria in 1932.
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Hydroxypethidine is under international control under the Single Convention on Narcotic Drugs 1961 and therefore controlled like morphine in most countries; in the United States it is a Schedule I Narcotic controlled substance with an ACSCN of 9627 and a 2014 annual aggregate manufacturing quota of 2 grams. The salt in use is the hydrochloride, with a free base conversion ratio of 0.878.
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Miotine is an anticholinesterase drug. Miotine was the first synthetic carbamate that was used clinically. Unlike the miotine analog neostigmine, it doesn't have a quaternary ammonium group to give it a permanent positive charge. It can exist as an uncharged free base which could allow it to cross the blood–brain barrier and cause unwanted central nervous system (CNS) side effects.
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Levorphanol is listed under the Single Convention On Narcotic Drugs 1961 and is regulated like morphine in most countries. In the U.S., it is a Schedule II Narcotic controlled substance with a DEA ACSCN of 9220 and 2013 annual aggregate manufacturing quota of 4.5 kilos. The salts in use are the tartrate (free base conversion ratio 0.58) and hydrobromide (0.76).
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The free base form of anti-cancer agent imatinib. Imatinib mesylate is a salt formed by a 1:1 reaction of imatinib and methanesulfonic acid.Before the High Court could decide on the issue of patentability, the Intellectual Property Appellate Board (IPAB) was formed and in 2007 the case was transferred before the IPAB in line with section 117G of the Indian Patent Act.
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As the thunderstorm moved into the southwest corner of Madison County at 4:15 p.m., the staff on duty at the WSO at Huntsville International Airport observed a wall cloud and rain-free base with the thunderstorm. The wall cloud showed no signs of rotation and dissipated shortly after being spotted. Shortly after this, between 4:20 and 4:30 p.m.
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Antimalarials are lipophilic weak bases and easily pass plasma membranes. The free base form accumulates in lysosomes (acidic cytoplasmic vesicles) and is then protonated, resulting in concentrations within lysosomes up to 1000 times higher than in culture media. This increases the pH of the lysosome from four to six. Alteration in pH causes inhibition of lysosomal acidic proteases causing a diminished proteolysis effect.
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The original synthesis at Janssen Pharmaceutica resulted in the preparation of a racemic mixture of two enantiomers, whose hydrochloride salt was reported to have a melting point of 264–265 °C; the free base of the racemate has a melting point of 87–89 °C. The racemic mixture is referred to as "tetramisole" - levamisole refers only to the levorotatory enantiomer of tetramisole.
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Route of deoxyribonolactone formation Hydrogen abstraction from the 1’-deoxyribose carbon by the hydroxyl radical creates a 1 ‘-deoxyribosyl radical. The radical can then react with molecular oxygen, creating a peroxyl radical which can be reduced and dehydrated to yield a 2’-deoxyribonolactone and free base. A deoxyribonolactone is mutagenic and resistant to repair enzymes. Thus, an abasic site is created.
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Anabasine is a structural isomer of nicotine, as both compounds have the molecular formula . Structure of protonated nicotine (left) and structure of the counterion benzoate (right). This combination is used in some vaping products to increase nicotine delivery to the lung. Pod mod electronic cigarettes use nicotine in the form of a protonated nicotine, rather than free-base nicotine found in earlier generations.
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Medicines in Japan which contain dihydrocodeine are coupled with caffeine to offset the sedative effects and discourage recreational use. Cough medicines containing dihydrocodeine are controlled similarly to dextromethrophan in the United States, in that its sale is strictly limited by purchase quantity and is restricted to persons 20 and older for purchase. ; United Kingdom : In the United Kingdom, dihydrocodeine is a Class B drug; but, it is available over- the-counter in small amounts (less than 8 mg), when combined with paracetamol (see co-dydramol). Dihydrocodeine is listed in Schedule 5 of the Misuse of Drugs Regulations 2001 whereby it is exempt from prohibition on possession provided that it is in the form of a single preparation not being designed for injection and less than 100 mg (calculated as free base) or with a total concentration less than 2.5% (calculated as free base).
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The heating accelerates the degradation of carbonic acid into carbon dioxide (CO2) and water. Loss of CO2 prevents the reaction from reversing back to cocaine hydrochloride. Free base cocaine separates as an oily layer, floating on the top of the now leftover aqueous phase. It is at this point that the oil is picked up rapidly, usually with a pin or long thin object.
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Manganism is also documented in reports of illicit methcathinone manufacturing. This is due to manganese being a byproduct of methcathinone synthesis if potassium permanganate is used as an oxidiser. Symptoms include apathy, bradykinesia, gait disorder with postural instability, and spastic-hypokinetic dysarthria. Another street drug sometimes contaminated with manganese is the so-called "Bazooka", prepared by free-base methods from cocaine using manganese carbonate.
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Manganism is also documented in reports of illicit methcathinone manufacturing. This is due to manganese being a byproduct of methcathinone synthesis if potassium permanganate is used as an oxidiser. Symptoms include apathy, bradykinesia, gait disorder with postural instability, and spastic- hypokinetic dysarthria. Another street drug sometimes contaminated with manganese is the so-called "Bazooka", prepared by free-base methods from cocaine using manganese carbonate.
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A few years, many women, and plenty of free-base pipes later, their lavish lifestyle begins to take its toll. The friends become dependent on cocaine and heroin. They also begin to distrust each other, and subsequent to an argument about the division of profit from a drug trade, Tony kidnaps Joakim's longtime girlfriend Helen. As Joakim becomes aware of the kidnapping, he begins searching for Tony.
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While drugs like dexamphetamine and methylphenidate are classified as Schedule II, pemoline is listed as Schedule IV (non-narcotic). In studies conducted on primates, pemoline fails to demonstrate a potential for self-administration. Pemoline is Schedule IV Non- Narcotic (Stimulant) controlled substance with a DEA ACSCN of 1530 and is not subject to annual manufacturing quotas. The salts in use are pemoline magnesium (free base conversion ratio .
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Butorphanol is listed under the Single Convention on Narcotic Drugs 1961 and in the United States is a Schedule IV Narcotic controlled substance with a DEA ACSCN of 9720; being in Schedule IV it is not subject to annual aggregate manufacturing quotas. The free base conversion ratio of the hydrochloride is 0.69. Butorphanol was originally in Schedule II and at one point it was decontrolled.
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A rotating wall cloud with rear flank downdraft clear slot evident to its left rear. Storm spotters are trained to discern whether a storm seen from a distance is a supercell. They typically look to its rear, the main region of updraft and inflow. Under the updraft is a rain-free base, and the next step of tornadogenesis is the formation of a rotating wall cloud.
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Uridine phosphorylase or pyrimidine-nucleoside phosphorylase adds ribose 1-phosphate to the free base uracil, forming uridine. Uridine kinase (aka uridine–cytidine kinase) can then phosphorylate this nucleoside into uridine monophosphate (UMP). UMP/CMP kinase () can phosphorylate UMP into uridine diphosphate, which nucleoside diphosphate kinase can phosphorylate into uridine triphosphate. Thymidine phosphorylase or pyrimidine-nucleoside phosphorylase adds 2-deoxy-alpha-D-ribose 1-phosphate to thymine, forming thymidine.
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Pemoline free base and pemoline cobalt, strontium, silver, barium, lithium, sodium, potassium, zinc, manganese, and caesium are research chemicals which can be produced in situ for experiments.DEA office of Diversion Control site: Federal Register publications of CSA schedules, 2014 Q1The A-Z Encyclopaedia of Alcohol and Drug AbuseCRC Handbook of Chemistry & Physics Others such as lanthanide pemoline salts such as pemoline cerium can be prepared; pemoline beryllium would presumably be toxic.
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The potency derives from the fact that it overlays fentanyl. Phenampromide produces similar effects to other opioids, including analgesia, sedation, dizziness and nausea. 4-Phenylphenampromide, PMID 3048547 Phenampromide is in Schedule I of the Controlled Substances Act 1970 of the United States as a Narcotic with ACSCN 9638 with a zero aggregate manufacturing quota as of 2014. The free base conversion ratio for salts includes 0.88 for the hydrochloride.
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Thebacon (INN; pronounced ), or dihydrocodeinone enol acetate, is a semisynthetic opioid that is similar to hydrocodone and is most commonly synthesised from thebaine. Thebacon is a derivative of acetyldihydrocodeine, where only the 6–7 double bond is saturated. Thebacon is marketed as its hydrochloride salt under the trade name Acedicon, and as its bitartrate under Diacodin and other trade names. The hydrochloride salt has a free base conversion ratio of 0.846.
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ACSCN tables include the CSA schedule, common alternative chemical and trade names, and the free base conversion ratio (the molecular mass of the substance in question divided by the molecular mass of the free base). This is used to make meaningful qualitative comparisons between substances, and labeling of the end product may, as is required in many European countries, list the active substance using both (e.g. "each tablet contains 120 mg dihydrocodeine bitartrate, representing 80 mg dihydrocodeine base"). This method of citation is in theory compulsory worldwide for substances in Schedule I of the Single Convention on Narcotic Drugs 1961, a classification corresponding to opioids in US Schedule II with Narcotic classification plus cocaine (which inherited a narcotic designation from the 1931 Convention for Limiting the Manufacture and Regulating the Distribution of Narcotic Drugs and preceding treaties and national laws including the 1914 Harrison Narcotics Tax Act) and German Betäubungsmittelgesetz (BtMG) Schedule I and so on.
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A nicotine base and a weak acid such as benzoic acid or levulinic acid is used to form a nicotine salt. Benzoic acid is the most used acid to create a nicotine salt. A free-base nicotine solution with an acid reduces the pH, which makes it possible to provide higher levels of nicotine without irritating the throat. Nicotine salts are thought to amplify the level and rate of nicotine delivery to the user.
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Properidine is an opioid, an analgesic, and the isopropyl analog of pethidine. Properidine is under international control and is listed in the United States under the Controlled Substances Act (1970) as a Schedule I substance. It is a narcotic, with an Administrative Controlled Substances Code Number (ACSCN) of 9644 and a 2 gramme annual aggregate manufacturing quota as of 2014. The salt in use is hydrochloride, with a free base conversion ratio of 0.88.
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An avicide is any substance (normally, a chemical) which can be used to kill birds. Commonly used avicides include strychnine, DRC-1339 (3-chloro-4-methylaniline hydrochloride, Starlicide) and CPTH (3-chloro-p- toluidine, the free base of Starlicide), and Avitrol (4-aminopyridine). Chloralose is also used as an avicide. In the past, highly concentrated formulations of parathion in diesel oil were also used, applied by aircraft spraying over the nesting colonies of the birds.
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Micromatabilin, the green pigment of the spider species Micrommata virescens, is characterized as a mixture of biliverdin conjugates. The two isolated fractions have identical absorption bands (free base: 620–630 μm, hydrochloride: 690 μm, zinc complex: 685–690 μm). Chromic acid degradation yields imides I, II, IIIa, and IIIb. Differences in the non-hydrolytic degradation and in polarity lead to the conclusion that fraction 1 is a monoconjugate and fraction 2a diconjugate of biliverdin.
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The dried residue is dissolved in sulfuric acid and the sulfate salt of veratridine is precipitated by dropwise addition of a solution of ammonium sulfate. Finally, the free base form is generated with ammonium hydroxide. An even better isolation of veratridine from veratrine is achieved using high- performance liquid chromatography (HPLC); as commercially available veratridine may vary in purity, HPLC purification of veratrine is a preferred method for isolation of veratridine for biological studies.
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It is a Schedule I Narcotic controlled substance in the United States, with a DEA ACSCN of 9613 and an annual aggregate manufacturing quota of zero as of 2013, and had been out of use in the United States for around a decade when the new Controlled Substances Act 1970 was promulgated. The salts of dextromoramide in use are the hydrochloride (free base conversion ratio 0.915) and tartrate (0.724). Racemoramide and moramide intermediate are also controlled.
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Bupropion: a cathinone derivative Cathinone can be extracted from Catha edulis, or synthesized from α-bromopropiophenone (which is easily made from propiophenone). Because cathinone is both a primary amine and a ketone, it is very likely to dimerize, especially as a free base isolated from plant matter. The structure of cathinone is very similar to that of other molecules. By reducing the ketone, it becomes cathine if it retains its stereochemistry, or norephedrine if its stereochemistry is inverted.
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Black tar heroin is a free base form of heroin that is sticky like tar or hard like coal. Its dark color is the result of crude processing methods that leave behind impurities. Black Tar as a type holds a variable admixture morphine derivatives—predominantly 6-MAM (6-monoacetylmorphine) which is another result of crude acetylation. The lack of proper reflux during acetylation fails to remove much of the moisture retained in the acetylating agent, glacial acetic acid.
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Illegal possession of dihydrocodeine can result in up to 5 years in prison or an unlimited fine. ; United States : In the US, dihydrocodeine is a DEA Schedule II substance, although preparations containing small amounts of dihydrocodeine are classified as Schedule III or Schedule V, depending on the concentration of dihydrocodeine relative to other active constituents, such as paracetamol (acetaminophen). This scheduling is similar to the UK's. The DEA's ACSCN for dihydrocodeine free base and all salts is 9120.
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Norcodeine is an opiate analogue that is the N-demethylated derivative of codeine. It has relatively little opioid activity in its own right, but is formed as a metabolite of codeine following ingestion. Norcodeine is a Schedule I Narcotic controlled substance in the US with the ACSCN of 9309 and zero annual manufacturing quota. The salts in use are the acetate (free base conversion ratio 0.826), hydroiodide (0.662), hydrochloride (0.759), nitrate (0.819), platinichloride (0.582), and sulphate (0.744).
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Pizza-eating contest The world's largest pizza was prepared in Rome in December 2012, and measured . The pizza was named "Ottavia" in homage to the first Roman emperor Octavian Augustus, and was made with a gluten-free base. The world's longest pizza was made in Fontana, California in 2017 and measured . The world's most expensive pizza listed by Guinness World Records is a commercially available thin-crust pizza at Maze restaurant in London, United Kingdom, which costs .
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There are pod mods that can be concealed in the palm of a person's hand. Later- generation pod mods are small like a Sharpie pen. Pod mods cost about half as much as larger e-cigarettes. The latest generation of e-cigarettes, "pod products", such as Juul, have the highest nicotine content (59 mg/mL), in protonated salt, rather than the free-base nicotine form found in earlier generations, which makes it easier for less experienced users to inhale.
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Amphetamine is a methyl homolog of the mammalian neurotransmitter phenethylamine with the chemical formula . The carbon atom adjacent to the primary amine is a stereogenic center, and amphetamine is composed of a racemic 1:1 mixture of two enantiomers. This racemic mixture can be separated into its optical isomers: levoamphetamine and dextroamphetamine. At room temperature, the pure free base of amphetamine is a mobile, colorless, and volatile liquid with a characteristically strong amine odor, and acrid, burning taste.
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Trimipramine is a tertiary amine TCA, with its side chain-demethylated metabolite desmethyltrimipramine being a secondary amine. Other tertiary amine TCAs include amitriptyline, imipramine, clomipramine, dosulepin (dothiepin), and doxepin. The chemical name of trimipramine is 3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-N,N,2-trimethylpropan-1-amine and its free base form has a chemical formula of C20H26N2 with a molecular weight of 294.434 g/mol. The drug is used commercially as the maleate salt.
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When they ran out of money, Boxleiter borrowed money from his parents, and eventually they both went homeless, living off of the couches of friends. Gasketball was released for iPad on August 9, 2012. They had decided to release the game as what they deemed to be an ethically non-coercive free-to-play game, with a free base game and in-app purchases for the extended content. Not as many players paid for the content as expected.
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A free-base nicotine solution with an acid reduces the pH, which makes it possible to provide higher levels of nicotine without irritating the throat. Nicotine salts are thought to amplify the level and rate of nicotine delivery to the user. The speed of nicotine salts uptake into the body with the use of electronic cigarettes is close to the speed of nicotine uptake from traditional cigarettes. Traditional cigarettes provide high levels of nicotine, but with the bad taste of smoking.
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The latest generation of e-cigarettes, "pod products," such as Juul, have the highest nicotine content (59 mg/mL), in protonated salt, rather than the free-base nicotine form found in earlier generations. In June 2015, Juul introduced a pod mod device containing nicotine salt. British American Tobacco stated that they have been using nicotine salts in their US Vuse e-liquid brand since 2012. There has been a proliferation of pod-based products with high nicotine concentration, triggered by Juul's financial success.
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Levomethorphan is listed under the Single Convention on Narcotic Drugs 1961 and is regulated like morphine in most countries. In the United States it is a Schedule II Narcotic controlled substance with a DEA ACSCN of 9210 and 2014 annual aggregate manufacturing quota of 195 grams, up from 6 grams the year before. The salts in use are the tartrate (free base conversion ratio 0.644) and hydrobromide (0.958). At the current time, no levomethorphan pharmaceuticals are marketed in the United States.
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Amphetamine (contracted from _a_ lpha- _m_ ethyl _ph_ en _et_ hyl _amine_ ) is a central nervous system (CNS) stimulant marketed under the brand name Evekeo, among others. It is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. Amphetamine was discovered in 1887 and exists as two enantiomers: levoamphetamine and dextroamphetamine. Amphetamine properly refers to a specific chemical, the racemic free base, which is equal parts of the two enantiomers, levoamphetamine and dextroamphetamine, in their pure amine forms.
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Lisuride, sold under the brand names Dopergin, Proclacam, and Revanil, is an antiparkinson agent of the iso-ergoline class, chemically related to the dopaminergic ergoline Parkinson's drugs. Lisuride is described as free base (see table on the right) and as hydrogen maleate salt. Lisuride is used to lower prolactin and, in low doses, to prevent migraine attacks. The use of lisuride as initial anti-Parkinsonian treatment has been advocated, delaying the need for levodopa until lisuride becomes insufficient for controlling the parkinsonian disability.
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MLA is soluble in chloroform, but does not dissolve well in water. The free base of MLA has not been obtained in crystalline form, and in its amorphous form it melts ultimately at 128 °C; the hydriodide salt has a melting point of 201 °C.; the perchlorate salt melts at 195 °C The citrate salt is the most common form in which MLA is currently available commercially.No citation is given here because the information is date-specific, and because it is inappropriate to endorse any particular supplier.
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Trimeperidine produces similar effects to other opioids, such as analgesia and sedation, along with side effects such as nausea, itching, vomiting and respiratory depression which may be harmful or fatal. Trimeperidine is in Schedule I of the Controlled Substances Act 1970 of the United States as a Narcotic with ACSCN 9646 with an annual aggregate manufacturing quota of 2 grammes as of 2014. The free base conversion ratio for salts includes 0.883 for the hydrochloride. Promedol increases the activity of the reticular activating system in the brain.
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Norpipanone (INN, BAN; Hexalgon) is an opioid analgesic related to methadone which was developed in Germany and distributed in Hungary, Argentina, and other countries. It had originally not been under international control but upon observation of case reports of addiction it was reviewed and shortly thereafter became a controlled substance. In the United States, it is a Schedule I controlled substance (ACSCN 9636, zero annual manufacturing quota as of 2014). The salts in use are the hydrobromide (free base conversion ratio 0.806) and hydrochloride (0.902).
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A rotating wall cloud with rear flank downdraft clear slot evident to its left rear Storm spotters are trained to discern whether or not a storm seen from a distance is a supercell. They typically look to its rear, the main region of updraft and inflow. Under that updraft is a rain-free base, and the next step of tornadogenesis is the formation of a rotating wall cloud. The vast majority of intense tornadoes occur with a wall cloud on the backside of a supercell.
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The smoking of cocaine base first appeared in the United States in 1974 and was mostly confined to the state of California. The first hospital admission for a problem related to free-basing was in 1975, the year in which extraction kits and smoking accessories became commercially available. In 1978, distribution of these accessories or paraphernalia spread from California throughout the United States. In 1979, only 1% of cocaine-related hospital admissions involved the use of free base, but by 1982 this figure had increased to 7%.
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Two grams of crack cocaine Crack cocaine, also known simply as crack or rock, is a free base form of cocaine that can be smoked. Crack offers a short, intense high to smokers. The Manual of Adolescent Substance Abuse Treatment calls it the most addictive form of cocaine. Crack first saw widespread use as a recreational drug in primarily impoverished neighborhoods in New York City, Philadelphia, Baltimore, Washington, D.C., Los Angeles, and Miami in late 1984 and 1985; its rapid increase in use and availability is sometimes termed as the "crack epidemic".
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The synthesis involves a non-metal reduction that is typically carried out in three steps. For amphetamine synthesis, a mixture of phenylacetone and formamide (sometimes in the presence of formic acid) or ammonium formate, is heated until a condensation reaction results in the intermediate product, formetamide. In the second step, formetamide is hydrolysed using hydrochloric acid, and the reaction mixture is then basified, isolated, and steam distilled to produce the free base. The final step, the product is dissolved in an organic solvent and precipitated as the sulphate salt of amphetamine by adding sulfuric acid.
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Side effects are similar to those of other opiates and include itching, nausea and respiratory depression. Related opioid analogues such as nicomorphine and nicodicodeine were first synthesized. The definitive synthesis, which involves treating anhydrous codeine base with nicotinic anhydride at 130 °C, was published by Pongratz and Zirm in Monatshefte für Chemie in 1957, simultaneously with the two analogues in an article about amides and esters of various organic acids. Nicocodeine is almost always used as the hydrochloride salt, which has a free base conversion ratio of .917.
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Pyrrolizidine alkaloids are a group of chemicals produced by plants as secondary metabolites, all of which contain a pyrrolizidine nucleus. This nucleus is made up of two pyrrole rings bonded by one carbon and one nitrogen. There are two forms in which PAs can exist and will readily interchange between: a pro-toxic free base form, also called a tertiary amine, or in a non-toxic form of N-oxide. Researchers have collected data that strongly suggests that PAs can be registered by taste receptors of predators, acting as a deterrent from being ingested.
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Racemoramide (INN, BAN), or simply moramide, is an opioid analgesic and a racemic mixture of the substances dextromoramide (the active component) and levomoramide (which is inactive), two enantiomers of a chiral molecule. Racemoramide is itself controlled; in the United States it is under Schedule I as a Narcotic with an ACSCN of 9645 and a zero annual aggregate manufacturing quota as of 2014. Its salts are the bitartrate (free base conversion ratio 0.723) and dihydrochloride (0.843) Moramide intermediate is listed separately as a Schedule II Narcotic controlled substance (ACSCN 9802), also with a zero quota.
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In the United States, it was never available and is classified as a Schedule I drug with a DEA ACSCN of 9301. The salts in use are the bitartrate (free base conversion ratio 0.643) and hydrochloride (0.770). The 2014 national aggregate manufacturing quota was 2 grams, unchanged from prior years. Hydromorphinol is metabolised mainly in the liver in the same fashion as many other opioids and is itself a minor active metabolite of 14-Hydroxydihydrocodeine, an uncommonly used opiate (but is therefore also an active metabolite of a first-order active metabolite of oxycodone).
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Nile blue in water. Left to right: pH 0, pH 4, pH 7, pH 10, pH 14\. Nile blue in water (lower phase) and ethyl acetate (upper phase) in daylight. Left to right: pH 0, pH 4, pH 7, pH 10, pH 14 Nile blue in water (lower phase) and ethyl acetate (upper phase) in UV light (366 nm). Left to right: pH 0, pH 4, pH 7, pH 10, pH 14 Nile blue (free base) in daylight (top row) and UV light (366 nm, bottom row) in different solvents.
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One synthesis of desomorphine from codeine Desomorphine has a molecular weight of 271.35 g/mol and three salts are known: hydrobromide (as in the original Permonid brand; free-base conversion ratio 0.770), hydrochloride (0.881) and sulfate (0.802). Its freebase form is slightly soluble in water (1.425 g/L at 25 °C), although its salts are very water-soluble; its freebase form is also very soluble in most polar organic solvents (like acetone, ethanol and ethyl acetate). Its melting point is 189 °C. It has a pKa of 9.69.
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It is available as the following salts, in approximate descending order of frequency of use: bitartrate, phosphate, hydrochloride, tartrate, hydroiodide, methyliodide, hydrobromide, sulfate, and thiocyanate. The salt to free base conversion factors are 0.67 for the bitartrate, 0.73 for the phosphate, and 0.89 for the hydrochloride. Dihydrocodeine is the parent drug of a series of moderately strong narcotics including, among others, hydrocodone, nicocodeine, nicodicodeine, thebaine and acetyldihydrocodeine. Whereas converting codeine to morphine is a difficult and unrewarding task, dihydrocodeine can be converted to dihydromorphine with very high yields (over 95%).
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The immediate-release and extended release variants of salts of both isomers reach peak plasma concentrations at 3 hours and 7 hours post-dose respectively. Amphetamine is eliminated via the kidneys, with of the drug being excreted unchanged at normal urinary pH. When the urinary pH is basic, amphetamine is in its free base form, so less is excreted. When urine pH is abnormal, the urinary recovery of amphetamine may range from a low of 1% to a high of 75%, depending mostly upon whether urine is too basic or acidic, respectively.
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It is similar to tramadol in its dual mechanism of action but unlike tramadol, it has much weaker effects on the reuptake of serotonin and is a significantly more potent opioid with no known active metabolites. Commercial preparations contain only the (R,R) stereoisomer, which is the weakest isomer in terms of opioid activity. The free base conversion ratio for salts includes 0.86 for the hydrochloride. The peak plasma concentration (Cmax; amount of active drug in the bloodstream) when taken after eating is increased by 8% and 18% for tapentadol IR and ER preparations, respectively.
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As well as its use as an analgesic, tilidine is also commonly used in Germany for treatment of restless legs syndrome. The reversed ester is also known and is also a prodrug. Tilidine is a controlled substance in most countries, listed in the German BtMG, Austrian SMG, and in the USA under the Controlled Substances Act 1970 as ACSCN 9750 as a Narcotic under Schedule I, with an annual aggregate manufacturing quota of 10 grams in 2014. It is used as the hydrochloride (free base conversion ratio 0.882) and HCl hemihydrate (0.858).
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In rainstorms, scud often form in the updraft area where the air has been cooled by precipitation from the downdraft, thus condensation occurs below the ambient cloud deck. If scud are rising and moving towards the main updraft, sometimes marked by a rain-free base (RFB) or wall cloud, then the thunderstorm is still developing from rising scud. In addition to forming in inflow, fractus also form in outflow. Scud are very common on the leading edge of a thunderstorm where warm, moist air is lifted by the gust front.
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The menu was tested over a 12-month period ahead of the launch. Eagle Boys told media it expected a 15% spike in sales on the back of the launch. A gluten "friendly" base was also on the menu for the first time, with an Eagle Boys spokesperson claiming it was more transparent than claiming it could offer a gluten-free base—only food prepared in a gluten-free kitchen can make the claim that it is truly offering a gluten free range. The chain also announced it would scale back its social media spend.
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Based on the intraperitoneal LD50 for rodents, at 74 mg per gram, it would require approximately 135 grams of beans to reach the estimated LD50of bufotenin for a 50 kg (110 lb) adult. Human intravenous tests using bufotenin suggest the LD50 may be much lower in humans with subjects showing signs of peripheral toxicity (purple face, tachycardia, difficulty breathing, etc.) at doses as little as 8 mg in some subjects.TiKHAL, Alexander Shulgin, 1997 Free base bufotenin when insufflated, taken sublingually, orally, or intrarectally, elicits strong hallucinogenic effects with far less side effects.
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In the UK, it is sold under the brand Heminevrin (AstraZeneca Pharmaceuticals). Other brand names include Nevrin in Romania, Distraneurin in Germany and Distraneurine in Spain. The drug is marketed either as a free base in an oily solution containing 192 mg in capsule form, or as clomethiazole edisylate syrup. Due to its high toxicity compared to similar drugs it is not recommended as a first-line treatment for any indication and is particularly dangerous to patients with an elevated risk for drug abuse such as those with a personal or familial history of addiction.
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Men at the time indicated that while they would consider switching to a filtered cigarette, they were concerned about being seen smoking a cigarette marketed to women. Part of Marlboro's rise in market share was its ability to produce "milder, more aromatic, sweeter, and less harsh" cigarettes by adding ammonia to the tobacco. Further usage of diammonium phosphate allowed Marlboro to free base the nicotine in tobacco, allowing for more efficient delivery. Marlboro kept this process secret for many years, as freebasing is the same process used to produce crack cocaine from normal cocaine.
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Diagram of supercell from above. RFD: rear flank downdraft, FFD: front flank downdraft, V: V-notch, U: Main Updraft, I: Updraft/Downdraft Interface, H: hook echo This is generally the area of heaviest and most widespread precipitation. For most supercells, the precipitation core is bounded on its leading edge by a shelf cloud that results from rain-cooled air within the precipitation core spreading outward and interacting with warmer, moist air from outside of the cell. Between the precipitation-free base and the FFD, a "vaulted" or "cathedral" feature can be observed.
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Cocaine hydrochloride ("powder cocaine"), for example, cannot be smoked, as it decomposes at the high temperatures produced by smoking. Free base cocaine, on the other hand, in which the cocaine alkaloid, which contains a nitrogen (which acts as a Lewis base) is "freed" from the hydrochloride salt, has a melting point of 98°C and is volatile (i.e. tends to vaporize) at temperatures above 90°C, and is therefore, unlike the hydrochloride salt, actively smokable. After inhalation the alkaloid is absorbed into the blood stream and rapidly transported throughout the body.
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It is approved for dogs in the United States, and distributed in the United States by Pfizer Animal Health and by Novartis Animal Health in Canada under the product name Domitor. Other alpha-two agonists used in veterinary medicine include xylazine and detomidine, but their use is less common in small animal surgery. The marketed product is a racemic mixture of two stereoisomers; dexmedetomidine is the isomer with more useful effects, and is now marketed as Dexdomitor. The free base form of medetomidine is sold as Selektope for use as an antifouling substance in marine paints.
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The resulting conjugated planar macrocycle may be substituted at the meso- and/or β-positions (2, 3, 7, 8, 12, 13, 17 and 18): if the meso- and β-hydrogens are substituted with non-hydrogen atoms or groups, the resulting compounds are known as porphyrins. The inner two protons of a free- base porphyrin can be removed by strong bases such as alkoxides, forming a dianionic molecule; conversely, the inner two pyrrolenine nitrogens can be protonated with acids such as trifluoroacetic acid affording a dicationic intermediate. The tetradentate anionic species can readily form complexes with most metals.
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Propylhexedrine is structurally similar to phenylethylamines, with the only structural difference being the substitution of an alicyclic cyclohexyl group for the aromatic phenyl group of phenethylamine. Propylhexedrine is not an amphetamine, nor even a phenethylamine, but instead can be referred to as a cycloalkylamine, or more specifically a cyclohexylethylamine being the N,a-dimethyl derivative of 2-cyclohexylethylamine. Propylhexedrine is a chiral compound (the α-carbon is chiral), and the active ingredient contained in Benzedrex inhalers is racemic (RS)-propylhexedrine as the free base. (S)-Propylhexedrine, also known as levopropylhexedrine, is believed to be the more biologically active isomer of the two.
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Nortriptyline is a tricyclic compound, specifically a dibenzocycloheptadiene, and possesses three rings fused together with a side chain attached in its chemical structure. Other dibenzocycloheptadiene TCAs include amitriptyline (N-methylnortriptyline), protriptyline, and butriptyline. Nortriptyline is a secondary amine TCA, with its N-methylated parent amitriptyline being a tertiary amine. Other secondary amine TCAs include desipramine and protriptyline. The chemical name of nortriptyline is 3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-N-methyl-1-propanamine and its free base form has a chemical formula of C19H21N1 with a molecular weight of 263.384 g/mol.
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The protonated form of methadone takes on an extended conformation, while the free base is more compact. In particular, it was found that there is an interaction between the tertiary amine and the carbonyl carbon of the ketone function (R3N ••• >C=O) that limits the molecule's conformation freedom, though the distance (291 pm by X-ray) is far too long to represent a true chemical bond. However, it does represent the initial trajectory of attack of an amine on a carbonyl group and was an important piece of experimental evidence for the proposal of the Bürgi–Dunitz angle for carbonyl addition reactions.
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The oral bioavailability of amphetamine varies with gastrointestinal pH; it is well absorbed from the gut, and bioavailability is typically over 75% for dextroamphetamine. Amphetamine is a weak base with a pKa of 9.9; consequently, when the pH is basic, more of the drug is in its lipid soluble free base form, and more is absorbed through the lipid-rich cell membranes of the gut epithelium. Conversely, an acidic pH means the drug is predominantly in a water-soluble cationic (salt) form, and less is absorbed. Approximately of amphetamine circulating in the bloodstream is bound to plasma proteins.
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Amitriptyline is a tricyclic compound, specifically a dibenzocycloheptadiene, and possesses three rings fused together with a side chain attached in its chemical structure. Other dibenzocycloheptadiene TCAs include nortriptyline (noramitriptyline, N-desmethylamitriptyline), protriptyline, and butriptyline. Amitriptyline is a tertiary amine TCA, with its side chain-demethylated metabolite nortriptyline being a secondary amine. Other tertiary amine TCAs include imipramine, clomipramine, dosulepin (dothiepin), doxepin, and trimipramine. The chemical name of amitriptyline is 3-(10,11-dihydro-5H-dibenzo[a,d]cycloheptene-5-ylidene)-N,N-dimethylpropan-1-amine and its free base form has a chemical formula of C20H23N with a molecular weight of 277.403 g/mol.
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The Fischer oxazole synthesis is a type of dehydration reaction which can occur under mild conditions in a rearrangement of the groups that would not seem possible. The reaction occurs by dissolving the reactants in dry ether and passing through the solution dry, gaseous hydrogen chloride. The product, which is the 2,5-disubstituted oxazole, precipitates as the hydrochloride and can be converted to the free base by the addition of water or by boiling with alcohol. The cyanohydrins and aldehydes used for the synthesis are usually aromatic, however there have been instances where aliphatic compounds have been used.
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Biosynthesis of choline in plants In plants, the first step in de novo biosynthesis of choline is the decarboxylation of serine into ethanolamine, which is catalyzed by a serine decarboxylase. The synthesis of choline from ethanolamine may take place in three parallel pathways, where three consecutive N-methylation steps catalyzed by a methyl transferase are carried out on either the free-base, phospho- bases, or phosphatidyl-bases. The source of the methyl group is S-adenosyl-- methionine and S-adenosyl--homocysteine is generated as a side product. Main pathways of choline (Chol) metabolism, synthesis and excretion.
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Desipramine is a tricyclic compound, specifically a dibenzazepine, and possesses three rings fused together with a side chain attached in its chemical structure. Other dibenzazepine TCAs include imipramine (N-methyldesipramine), clomipramine, trimipramine, and lofepramine (N-(4-chlorobenzoylmethyl)desipramine). Desipramine is a secondary amine TCA, with its N-methylated parent imipramine being a tertiary amine. Other secondary amine TCAs include nortriptyline and protriptyline. The chemical name of desipramine is 3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-N-methylpropan-1-amine and its free base form has a chemical formula of C18H22N2 with a molecular weight of 266.381 g/mol.
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Second-generation devices are larger overall and look less like traditional cigarettes. Third-generation devices include mechanical mods and variable voltage devices. The fourth- generation includes Sub ohm tanks (meaning that they have electrical resistance of less than 1 Ohm) and temperature control devices. The voltage for first-generation e-cigarettes is about 3.7 and second-generation e-cigarettes can be adjusted from 3 V to 6 V, while more recent devices can go up to 8 V. There are also pod mod devices that use protonated nicotine, rather than free-base nicotine found in earlier generations, providing higher nicotine yields through the production of aerosolized protonated nicotine.
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Metazocine is an opioid analgesic related to pentazocine. While metazocine has significant analgesic effects, mediated through a mixed agonist–antagonist action at the mu opioid receptor, its clinical use is limited by dysphoric and hallucinogenic effects which are most likely caused by activity at kappa opioid receptors (where it is a high-efficacy agonist) and/or sigma receptors. Metazocine is in Schedule II of the Controlled Substances Act 1970 of the United States as a Narcotic with ACSCN 9240 with a 19 gram aggregate manufacturing quota as of 2014. The free base conversion ratio for salts includes 0.81 for the hydrochloride and 0.74 for the hydrobromide.
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In the US, desomorphine is a Schedule 1 controlled substance, indicating that the United States FDA has determined that there are no legal medicinal uses for desomorphine in the U.S. It has maintained this status as a controlled substance in the United States since 1936. The drug is a Narcotic in Schedule I of the Controlled Substances Act 1970 of the United States as drug number (ACSCN) 9055. It is therefore subject to annual aggregate manufacturing quotas in the United States, and in 2014 the quota for desomorphine was 5 grams. It is produced as a hydrochloride (free base conversion ratio 0.85) and sulphate (0.80).
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The patent does not specify any crystal forms of the compounds or discuss their relative advantages and disadvantages.US Patent 5,521,184EP0564409 On 18 July 1997, Novartis filed a new patent application in Switzerland on the beta crystalline form of imatinib mesylate (the mesylate salt of imatinib). The "beta crystalline form" of the molecule is a specific polymorph of imatinib mesylate; a specific way that the individual molecules pack together to form a solid. This is the actual form of the drug sold as Gleevec/Glivec; a salt (imatinib mesylate) as opposed to a free base, and the beta crystalline form as opposed to the alpha or other form.Staff, European Medicines Agency, 2004.
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For constant pain, the relieving effect of extended-release morphine given once (for Kadian) or twice (for MS Contin) every 24 hours is roughly the same as multiple administrations of immediate release (or "regular") morphine. Morphine sulfate pentahydrade (trade names including Dolcontin) has a higher molecular mass than morphine base, and therefore 10 mg morphine sulfate pentahydrate contains approximatively 7.5 mg of morphine free base. Translated from Swedish "Morfinsulfatpentahydrat 10 mg motsvarande morfin 7,5 mg" Extended-release morphine can be administered together with "rescue doses" of immediate-release morphine pro re nata in case of breakthrough pain, each generally consisting of 5% to 15% of the 24-hour extended-release dosage.
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Oxycodone/aspirin (trade name Percodan) is a combination drug marketed by Endo Pharmaceuticals. It is a tablet containing a mixture of 325 mg (5 grains) of aspirin and 4.8355 mg of oxycodone HCl (equivalent to 4.3346 mg of oxycodone as the free base); it is an opioid/non-opioid combination used to treat moderate to moderately severe pain. The safety of the combination during pregnancy has not been established, although aspirin is generally contraindicated during pregnancy, and the drug has been placed in pregnancy category D. Inactive ingredients include D&C; Yellow 10, FD&C; Yellow 6, microcrystalline cellulose, and corn starch. Percodan was first marketed by DuPont Pharmaceuticals and prescribed in the United States in 1950.
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Cocaine base/crack can be smoked because it vaporizes with little or no decomposition at , which is below the boiling point of water. Crack is a lower purity form of free-base cocaine that is usually produced by neutralization of cocaine hydrochloride with a solution of baking soda (sodium bicarbonate, NaHCO3) and water, producing a very hard/brittle, off-white-to-brown colored, amorphous material that contains sodium carbonate, entrapped water, and other by-products as the main impurities. The origin of the name "crack" comes from the "crackling" sound (and hence the onomatopoeic moniker "crack") that is produced when the cocaine and its impurities (i.e. water, sodium bicarbonate) are heated past the point of vaporization.
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Metopon (5-methylhydromorphone)US Patent 2178010 is an opioid analogue that is a methylated derivative of hydromorphone which was invented in 1929 as an analgesic. Metopon is sometimes used in medicine, although longer acting than hydromorphone, Metopon is less potent and its oral bioavailability is fairly low. Generally, Metopon has few advantages to distinguish it from other, more commonly used opioid analgesics, although it does have a slightly lower tendency to produce nausea and respiratory depression compared to morphine. In Canada, as of 1948, the hydrochloride of metopon (free base conversion ratio 0.891, molecular weight 335.8) was available only for oral administration for malignant pain and for maintenance of those habituated to morphine; the only dosage form available was singly scored 8 mg tablets.
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In 1941, the USA was given 99-year free base rights in Bermuda, and began construction of a Naval Air Station, the Naval Operating Base (NOB), for flying boats, and an airfield for landplanes. The terms of the agreement were that the US-built airfield, on British territory, would be a joint US Army/Royal Air Force base. When the airfield (named Kindley Field after an American aviator who had fought for Britain during World War I) became operational in 1943, RAF Transport Command relocated to it, taking over the West end of the base in Castle Harbour. With the entry of the USA into the War, at the end of 1941, the US Navy began operating air-patrols from the Island.
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Because special names exist for benzene rings modified with one or two of these functional groups, several synonymous chemical names may be encountered: 3-chloro-4-methylaniline or 3-chloro-4-methylbenzenamine, 2-chloro-4-aminotoluene, or 3-chloro-p-toluidine. Numbered groups (2-chloro, 4-amino) also may be named out of order; the numbers of such groups equal the number of carbon atoms in the benzene ring separating them from the group implied in the special name. Preparations of this chemical may be named as a hydrochloride (e.g. "3-chloro-p-toluidine hydrochloride", CPTH), indicating that hydrochloric acid has been used to neutralize the molecule to a salt in which the amine group is protonated and a chloride counterion is present; otherwise the free base is indicated.
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In the early 1990s a number of derivatives of N-phenyl-2-pyrimidineamine were synthesized by scientists at Ciba-Geigy (now part of Novartis), one compound of which was CGP 57148 in free base form (later given the International Nonproprietary Name ‘imatinib’ by the World Health Organization (WHO)). A Swiss patent application was filed on 3 April 1992, which was then filed in the EU, the US, and other countries in March and April 1993US Patent Application No. 08/042,322). This application was abandoned and another continuation-in-part application was then filed on 28 April 1994 which matured into (US Patent 5,521,184).See here for worldwide filings] and in 1996 United States and European patent offices granted a patent to Novartis claiming imatinib and its derivatives, including salts thereof (but not mentioning mesylate).
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Porphyrin's highly conjugated skeleton produces a characteristic ultra-violet visible (UV-VIS) spectrum. The spectrum typically consists of an intense, narrow absorption band (ε > 200000 l mol−1 cm−1) at around 400 nm, known as the Soret band or B band, followed by four longer wavelength (450–700 nm), weaker absorptions (ε > 20000 L⋅mol−1⋅cm−1 (free-base porphyrins)) referred to as the Q bands. The Soret band arises from a strong electronic transition from the ground state to the second excited singlet state (S0 → S2); whereas the Q band is a result of a weak transition to the first excited singlet state (S0 → S1). The dissipation of energy via internal conversion (IC) is so rapid that fluorescence is only observed from depopulation of the first excited singlet state to the lower- energy ground state (S1 → S0).
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Novartis v UoI, Para 187, 188 However, as no material had been offered to indicate that the beta crystalline form of imatinib mesylate will produce an enhanced or superior efficacy (therapeutic) on molecular basis than what could be achieved with imatinib free base in vivo animal model, the court opined that the beta crystalline form of imatinib mesylate, does not qualify the test of Section 3(d).Novartis v UoI, Para 189, 191Novartis A.G. v. UOI & Ors. – Hon’ble Justice Aftab Alam’s Swansong, Rudrajyoti Nath Ray, RDA, 8 April 2013 Thus in effect, Indian Supreme Court upheld the view that under Indian Patent Act for grant of pharmaceutical patents apart from proving the traditional tests of novelty, inventive step and application, there is a new test of enhanced therapeutic efficacy for claims that cover incremental changes to existing drugs.
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Two songs from their self-titled debut album, which had Matthew on vocals and Cobrin on drums, piano, guitar and composition, were included in feature film soundtracks. "Hold Me" was in 2004's The Last Run, directed by Jonathan Segal and starring Fred Savage, and "Could Ya" appeared in the 2005 film Splinter, directed by Kai Maurer. After the dissolution of Elva Snow, Matthew performed with the band, Songs to Drink and Drive By, under the free-base mp3 label Comfort Stand. The group includes Matthew and Peter Gingerich on vocals with Marisol Limon on electronic organ, Nate Calkins on drums and Pablo Mitas on viola. Scott Matthew (2008) From 2001, Matthew provided vocals on the soundtracks of the anime film Cowboy Bebop: Knockin' on Heaven's Door (2001) and anime series Ghost in the Shell: Stand Alone Complex (2002–03).
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Amifampridine (pyridine-3,4-diamine, 3,4-diaminopyridine, 3,4-DAP) is used as a drug, predominantly in the treatment of a number of rare muscle diseases. The free base form of the drug has been used to treat congenital myasthenic syndromes and Lambert–Eaton myasthenic syndrome (LEMS) through compassionate use programs since the 1990s and was recommended as a first line treatment for LEMS in 2006, using ad hoc forms of the drug, since there was no marketed form. Around 2000 doctors at Assistance Publique – Hôpitaux de Paris created a phosphate salt form, which was developed through a series of companies ending with BioMarin Pharmaceutical which obtained European approval in 2009 under the trade name Firdapse, and which licensed the US rights to Catalyst Pharmaceuticals in 2012. As of January 2017, Catalyst and another US company, Jacobus Pharmaceutical, which had been manufacturing and giving it away for free since the 1990s, were both seeking FDA approval for their iterations and marketing rights.
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To prove novelty and inventive step it was argued that the Zimmermann patent did not teach or suggest to a person skilled in the art to select the beta crystalline form in preference to other compounds of which examples were given in the Zimmermann patent. Further, even if the beta crystalline form was selected, the Zimmermann patent did not teach a person to how to prepare that particular polymorph of the salt. Having arrived at the beta crystal form of methanesulfonic acid addition salt (mesylate salt) of imatinib, Novartis contended that the inventors had to further research to be able to ensure that particular salt form of imatinib was suitable for administration in a solid oral dosage form. Hence, the coming into being of the beta crystalline form of imatinib mesylate from the free base of imatinib was the result of an invention that involved technical advance as compared to the existing knowledge and brought into existence a new substance.
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In 2007 the drug's international nonproprietary name was published by the WHO. In the face of the 7 year exclusivity that an orphan approval would give to Biomarin, and of the increase in price that would accompany it, Jacobus began racing to conduct formal clinical trials in order to get approval for the free base form before BioMarin; its first Phase II trial was opened in January 2012. In October 2012, while BioMarin had a Phase III trial ongoing in the US, it licensed the US rights to 3,4-DAPP, including the orphan designation and the ongoing trial, to Catalyst Pharmaceuticals. Catalyst anticipated that it could earn $300 to $900 million per year in sales at peak sales for treatment of people with LEMS and other indications, and analysts anticipated the drug would be priced at around. $100,000 in the US. Catalyst went on to obtain a breakthrough therapy designation for 3,4-DAPP in LEMS in 2013, an orphan designation for congenital myasthenic syndromes in 2015 and an orphan designation for myasthenia gravis in 2016.
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