Toxicokinetics of Amphetamines: Metabolism and Toxicokinetic Data of Designer Drugs, Amphetamine, Methamphetamine, and Their N-Alkyl Derivatives

Amphetamines and related designer drugs are metabolized primarily by cytochrome P450 enzymes, with many N-alkylated derivatives acting as prodrugs that convert to active amphetamine or methamphetamine. The review covers MDA, MDMA, MDE, BDB, MBDB, and several N-alkylated amphetamines including methamphetamine, benzphetamine, and selegiline. It summarizes findings from English-language publications between 1995 and 2000 on metabolite identification, cytochrome P450-dependent metabolism, and pharmacokinetic or toxicokinetic data. The implications of these toxicokinetic pathways for forensic toxicology and interpretation in legal cases are discussed.

Study at a glance

Abstract

This paper reviews the toxicokinetics of amphetamines. The designer drugs MDA (methylenedioxy-amphetamine, R,S-1-(3;,4;-methylenedioxyphenyl)2-propanamine), MDMA (R,S-methylenedioxymethamphetamine), and MDE (R,S-methylenedioxyethylamphetamine), as well as BDB (benzodioxolylbutanamine; R,S-1-(1;,3;-benzodioxol-5;-yl)-2-butanamine or R,S-1-(3;,4;-methylenedioxyphenyl)-2-butanamine) and MBDB (R,S-N-methyl-benzodioxolylbutanamine), were taken into consideration, as were the following N-alkylated amphetamine derivatives: amphetaminil, benzphetamine, clobenzorex, dimethylamphetamine, ethylamphetamine, famprofazone, fencamine, fenethylline, fenproporex, furfenorex, mefenorex, mesocarb, methamphetamine, prenylamine, and selegiline. English-language publications from 1995 to 2000 were reviewed. Papers describing identification of metabolites or cytochrome P450 isoenzyme-dependent metabolism and papers containing pharmacokinetic/toxicokinetic data were considered and summarized. The implications of toxicokinetics for toxicologic assessment or for interpretation in forensic cases are discussed.