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ECHA InfoCard | 100.164.420 |
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Formula | C9H10N2O |
Molar mass | 162.192 g·mol−1 |
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Chirality | Racemic mixture |
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Aminorex (Menocil, Apiquel, aminoxaphen, aminoxafen, McN-742) is a weight loss (anorectic) stimulant drug. It was withdrawn from the market after it was found to cause pulmonary hypertension. [2] In the U.S., it is an illegal Schedule I drug, meaning it has high abuse potential, no accepted medical use, and a poor safety profile.
Aminorex, in the 2-amino-5-aryl oxazoline class, was developed by McNeil Laboratories in 1962. [3] It is closely related to 4-methylaminorex. Aminorex has been shown to have locomotor stimulant effects, lying midway between dextroamphetamine and methamphetamine. Aminorex effects have been attributed to the release of catecholamines. [4] It can be produced as a metabolite of the worming medication levamisole, which is sometimes used as a cutting agent of illicitly produced cocaine. [5] [6]
Aminorex has been found to act as a reuptake inhibitor at the dopamine and norepinephrine transporters, with releasing agent properties at the serotonin transporter. [7]
It was discovered in 1962 by Edward John Hurlburt, [8] and was quickly found in 1963 to have an anorectic effect in rats. It was introduced as a prescription appetite suppressant in Germany, Switzerland and Austria in 1965, but was withdrawn in 1972 after it was found to cause pulmonary hypertension in approximately 0.2% of patients, and was linked to a number of deaths. [4] [9]
The synthesis was first reported in a structure-activity relationship study of 2-amino-5-aryl-2-oxazolines, where aminorex was found to be approximately 2.5 times more potent than D-amphetamine sulfate in inducing anorexia in rats, and was also reported to have CNS stimulant effects.
The racemic synthesis involves addition/cyclization reaction of 2-amino-1-phenylethanol with cyanogen bromide. [10] A similar synthesis has been also published. [11] In a search for a cheaper synthetic route, a German team developed an alternative route [12] which, by using chiral styrene oxide, allows an enantiopure product.
Phenethylamine (PEA) is an organic compound, natural monoamine alkaloid, and trace amine, which acts as a central nervous system stimulant in humans. In the brain, phenethylamine regulates monoamine neurotransmission by binding to trace amine-associated receptor 1 (TAAR1) and inhibiting vesicular monoamine transporter 2 (VMAT2) in monoamine neurons. To a lesser extent, it also acts as a neurotransmitter in the human central nervous system. In mammals, phenethylamine is produced from the amino acid L-phenylalanine by the enzyme aromatic L-amino acid decarboxylase via enzymatic decarboxylation. In addition to its presence in mammals, phenethylamine is found in many other organisms and foods, such as chocolate, especially after microbial fermentation.
An anorectic or anorexic is a drug which reduces appetite, resulting in lower food consumption, leading to weight loss. These substances work by affecting the central nervous system or certain neurotransmitters to create a feeling of fullness or reduce the desire to eat. The understanding of anorexiant effects is crucial in the development of interventions for weight management, eating disorders, and related health concerns. The anorexiant effect can be induced through diverse mechanisms, ranging from hormonal regulation to neural signaling. Ghrelin, leptin, and peptide YY are among the hormones involved in appetite control. Additionally, neurotransmitters such as serotonin and dopamine in the central nervous system contribute significantly to the regulation of food intake.
Phendimetrazine is a stimulant drug of the morpholine chemical class used as an appetite suppressant.
Phenmetrazine is a stimulant drug first synthesized in 1952 and originally used as an appetite suppressant, but withdrawn from the market in the 1980s due to widespread abuse. It was initially replaced by its analogue phendimetrazine which functions as a prodrug to phenmetrazine, but now it is rarely prescribed, due to concerns of abuse and addiction. Chemically, phenmetrazine is a substituted amphetamine containing a morpholine ring.
Phenylacetone, also known as phenyl-2-propanone, is an organic compound with the chemical formula C6H5CH2COCH3. It is a colorless oil that is soluble in organic solvents. It is a mono-substituted benzene derivative, consisting of an acetone attached to a phenyl group. As such, its systematic IUPAC name is 1-phenyl-2-propanone.
4-Methylaminorex is a stimulant drug of the 2-amino-5-aryloxazoline class that was first synthesized in 1960 by McNeil Laboratories. It is also known by its street name "U4Euh" ("Euphoria"). It is banned in many countries as a stimulant.
Levamisole, sold under the brand name Ergamisol among others, is a medication used to treat parasitic worm infections, specifically ascariasis and hookworm infections. It is taken by mouth.
Chlorphentermine is a serotonergic appetite suppressant of the amphetamine family. Developed in 1962, it is the 4-chloro derivative of the better known appetite suppressant phentermine, which is still in current use.
Mazindol is a stimulant drug which is used as an appetite suppressant. It was developed by Sandoz-Wander in the 1960s.
Benfluorex, sold under the brand name Mediator, is an anorectic and hypolipidemic agent that is structurally related to fenfluramine. It may improve glycemic control and decrease insulin resistance in people with poorly controlled type-2 diabetes.
Thozalinone (USAN) is a psychostimulant that has been used as an antidepressant in Europe. It has also been trialed as an anorectic. Thozalinone is described as a "dopaminergic stimulant", and likely acts via inducing the release of dopamine and to a minimal extent norepinephrine; similar to analogue pemoline, it is reportedly devoid of abuse potential unlike other dopaminergic psychostimulants.
Fluminorex is a centrally acting sympathomimetic which is related to other drugs such as aminorex and pemoline. It was developed as an appetite suppressant by McNeil Laboratories in the 1950s.
Cyclazodone is a centrally acting stimulant drug developed by American Cyanamid Company in the 1960s. The drug is related to other drugs such as pemoline and thozalinone. It displayed a favorable therapeutic index and margin of safety in comparison to Pemoline and other N-lower-alkyl-substituted Pemoline derivatives. The patents concluded that Cyclazodone possessed properties efficacious in reducing fatigue and as a potential anorectic. Structural congeners of Pemoline have been described as "excitants with unique properties distinguishing them from the sympathomimetic amines" whilst displaying less stimulatory activity and toxicity compared to amphetamine.
A monoamine releasing agent (MRA), or simply monoamine releaser, is a drug that induces the release of a monoamine neurotransmitter from the presynaptic neuron into the synapse, leading to an increase in the extracellular concentrations of the neurotransmitter. Many drugs induce their effects in the body and/or brain via the release of monoamine neurotransmitters, e.g., trace amines, many substituted amphetamines, and related compounds.
Cloforex (Oberex) is an anorectic of the amphetamine class. It is a prodrug to chlorphentermine. It never became a mass produced drug in part due to the side effects found in mice. Mice who consumed 75 mg of cloforex a day experienced weight loss along with pulmonary hypertension and hair loss.
Difemetorex is a stimulant drug of the piperidine class which was used as an appetite suppressant, but produced intolerable side effects such as insomnia which limited its clinical use. It was introduced in France by Ciba-Geigy in 1966 but is now no longer marketed.
p-Hydroxynorephedrine (PHN), or 4-hydroxynorephedrine, is the para-hydroxy analog of norephedrine and an active sympathomimetic metabolite of amphetamine in humans. When it occurs as a metabolite of amphetamine, it is produced from both p-hydroxyamphetamine and norephedrine.
4-Hydroxyphenylacetone is the para-hydroxy analog of phenylacetone, an inactive metabolite of amphetamine in humans. When it occurs as a metabolite of amphetamine, it is produced directly from the inactive metabolite phenylacetone.
Substituted phenylmorpholines, or substituted phenmetrazines alternatively, are chemical derivatives of phenylmorpholine or of the psychostimulant drug phenmetrazine. Most such compounds act as releasers of monoamine neurotransmitters, and have stimulant effects. Some also act as agonists at serotonin receptors, and compounds with an N-propyl substitution act as dopamine receptor agonists. A number of derivatives from this class have been investigated for medical applications, such as for use as anorectics or medications for the treatment of ADHD. Some compounds have also become subject to illicit use as designer drugs.