Interaction of 3,4-methylenedioxymethamphetamine and methamphetamine during metabolism by in vitro human metabolic enzymes and in rats.
Illicit amphetamine-type stimulant (ATS) tablets commonly contain one or more active ingredients, which have hallucinogenic and/or stimulant effects. Because components such as 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine (MA) in ATS tablets have similar chemical structures, they could be metabolized by common metabolic enzymes. To investigate potential metabolic interactions of ATS tablet components, we studied the in vitro metabolism of MDMA and MA using human metabolic enzymes. MDMA and MA were mainly metabolized by cytochrome P450 2D6 (CYP2D6) and mutually inhibited the production of their main metabolites. In vivo experiments were also performed using intravenous administration of MDMA, MA, or their mixture to rats. The plasma concentrations of MDMA and MA after co-administration were higher than those after administration of MDMA or MA alone. The results in this study imply that multiple components in ATS tablets can interact to mutually inhibit their metabolism and potentially enhance the toxicity of each component.
National Research Institute of Police Science, Kashiwa, Chiba, Japan. kuwayama@nrips.go.jp
Kenji
K
Kuwayama
Kenji
K
Tsujikawa
Hajime
H
Miyaguchi
Tatsuyuki
T
Kanamori
Yuko T
YT
Iwata
Hiroyuki
H
Inoue
D000818:Animals; D001711:Biotransformation; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D004347:Drug Interactions; D053593:Forensic Toxicology; D006213:Hallucinogens / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008694:Methamphetamine / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*; D008861:Microsomes / Q000378:metabolism; D008995:Monoamine Oxidase / Q000378:metabolism; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000097:blood / Q000493:pharmacokinetics*; D010105:Oxygenases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D006213:Hallucinogens; C079646:4-hydroxy-3-methoxymethamphetamine; D008694:Methamphetamine; C005877:pholedrine; D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming); D019389:Cytochrome P-450 CYP2D6; D008995:Monoamine Oxidase; D018817:N-Methyl-3,4-methylenedioxyamphetamine