Toxicity of amphetamines: an update

• Published in: Archives of toxicology 2012-08, Vol.86 (8), p.1167-1231
• Main Authors: Carvalho, Marcia, Carmo, Helena, Costa, Vera Marisa, Capela, João Paulo, Pontes, Helena, Remião, Fernando, Carvalho, Félix, Bastos, Maria de Lourdes
• Format: Article
• Language: English
• Subjects: Acids; Amphetamine; Amphetamine - chemistry; Amphetamine - pharmacokinetics; Amphetamine - toxicity; Amphetamine-Related Disorders - complications; Amphetamine-Related Disorders - genetics; Amphetamine-Related Disorders - metabolism; Amphetamines; Animals; Biomedical and Life Sciences; Biomedicine; Cardiovascular toxicity; Central Nervous System Stimulants - chemistry; Central Nervous System Stimulants - pharmacokinetics; Central Nervous System Stimulants - toxicity; Chemical and Drug Induced Liver Injury - etiology; Dopamine; Ecstasy; Environmental Health; Ephedra; Genetic Predisposition to Disease; Heart Diseases - chemically induced; Hepatotoxicity; Humans; Hyperthermia; Kidney Diseases - chemically induced; Kinases; Methamphetamine; Nephrotoxicity; Neurotoxicity; Neurotoxicity Syndromes - etiology; Occupational Medicine/Industrial Medicine; Oxidative stress; Pharmacokinetics; Pharmacology/Toxicology; Review Article; Rhabdomyolysis; Rhabdomyolysis - chemically induced; Risk Assessment; Risk Factors; Serotonin; Toxicity
• ISSN: 0340-5761; 1432-0738
• DOI: 10.1007/s00204-012-0815-5

Amphetamines represent a class of psychotropic compounds, widely abused for their stimulant, euphoric, anorectic, and, in some cases, emphathogenic, entactogenic, and hallucinogenic properties. These compounds derive from the β-phenylethylamine core structure and are kinetically and dynamically characterized by easily crossing the blood-brain barrier, to resist brain biotransformation and to release monoamine neurotransmitters from nerve endings. Although amphetamines are widely acknowledged as synthetic drugs, of which amphetamine, methamphetamine, and 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) are well-known examples, humans have used natural amphetamines for several millenniums, through the consumption of amphetamines produced in plants, namely cathinone (khat), obtained from the plant Catha edulis and ephedrine, obtained from various plants in the genus Ephedra. More recently, a wave of new amphetamines has emerged in the market, mainly constituted of cathinone derivatives, including mephedrone, methylone, methedrone, and buthylone, among others. Although intoxications by amphetamines continue to be common causes of emergency department and hospital admissions, it is frequent to find the sophism that amphetamine derivatives, namely those appearing more recently, are relatively safe. However, human intoxications by these drugs are increasingly being reported, with similar patterns compared to those previously seen with classical amphetamines. That is not surprising, considering the similar structures and mechanisms of action among the different amphetamines, conferring similar toxicokinetic and toxicological profiles to these compounds. The aim of the present review is to give an insight into the pharmacokinetics, general mechanisms of biological and toxicological actions, and the main target organs for the toxicity of amphetamines. Although there is still scarce knowledge from novel amphetamines to draw mechanistic insights, the long-studied classical amphetamines-amphetamine itself, as well as methamphetamine and MDMA, provide plenty of data that may be useful to predict toxicological outcome to improvident abusers and are for that reason the main focus of this review.