DARK Classics in Chemical Neuroscience: Aminorex Analogues.

Aminorex (5-phenyl-4,5-dihydro-1,3-oxazol-2-amine) and 4-methylaminorex (4-methyl-5-phenyl-4,5-dihydro-1,3-oxazol-2-amine) are psychostimulants that have long been listed in Schedules IV and I of the UN Convention on Psychotropic Substances of 1971. However, a range of psychoactive analogues exist that are not internationally controlled and therefore often classified as new psychoactive substances (NPS). Aminorex analogues encompass failed pharmaceuticals that reemerged as drugs of abuse, and newly synthesized substances that were solely designed for recreational use by clandestine chemists. NPS, sometimes also referred to as "designer drugs" in alignment with a phenomenon arising in the early 1980s, serve as alternatives to controlled drugs. Aminorex and its derivatives interact with monoaminergic neurotransmission by interfering with the function of monoamine transporters. Hence, these compounds share pharmacological and neurochemical similarities with amphetamines and cocaine. The consumption of aminorex, 4-methylaminorex and 4,4'-dimethylaminorex (4-methyl-5-(4-methylphenyl)-4,5-dihydro-1,3-oxazol-2-amine) has been associated with adverse events including death, bestowing an inglorious fame on aminorex-derived drugs. In this Review, a historical background is presented, as well as an account of the pharmacodynamic and pharmacokinetic properties of aminorex and various analogues. Light is shed on their misuse as drug adulterants of well-established drugs on the market. This Review not only provides a detailed overview of an abused substance-class, but also emphasizes the darkest aspect of the NPS market, i.e., deleterious side effects that arise from the ingestion of certain NPS, as knowledge of the pharmacology, the potency, or the identity of the active ingredients remains obscure to NPS users.

The formation of aminorex in racehorses following levamisole administration. A quantitative and chiral analysis following synthetic aminorex or levamisole administration vs. aminorex-positive samples from the field: a preliminary report.

Beginning in 2004, the horseracing industry experienced an epidemic of drug positives for the amphetamine-like drug aminorex. Investigation of the therapeutic treatment of the horses called positive for this drug suggested that its source was from the administration of the anthelmintic levamisole. This study examines the urine concentrations of aminorex as a function of time following administration of synthetic, racemic aminorex. Confirmation of the presence of aminorex in urine samples from the horses known to be treated with levamisole is also presented as are data concerning the concentrations of aminorex in positives called from the field and the corresponding concentrations of levamisole found in the same samples. Furthermore, this study illustrates that the chiral isomer distribution of aminorex found in samples from the field is significantly different from that arising from the administration of synthetic, racemic aminorex and is similar to that observed from aminorex arising from levamisole administration. An examination of the chiral isomer distribution of aminorex and a determination of the presence of levamisole in a sample may be used to assess the source of an aminorex positive, distinguishing it from an intentional synthetic, racemic aminorex administration. The role of levamisole in aminorex formation is also discussed.

[Drug induced pulmonary hypertension].

Primary pulmonary hypertension (PPH) is a rare, often fatal disease that tends to occur with particular frequency in woman. The factors leading to its development remain enigmatic. A variety of toxins and drugs have been implicated in the pathogenesis of pulmonary hypertension (PH). In the 1960s, the medical community was first alerted to the problem of an epidemic of PH in association with a particular anorexic agent, aminorex. Recent reports have indicated that anorexic drugs may have causative roles in PH. The International Primary Pulmonary Hypertension Study (IPPHS) showed a strong association between PPH and the use of appetite suppressants. But the mechanism by which these anorectic drugs cause PH is unknown.