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Interaction of 3,4‐Methylenedioxymethamphetamine and Methamphetamine During Metabolism by In Vitro Human Metabolic Enzymes and in Rats *
Author(s) -
Kuwayama Kenji,
Tsujikawa Kenji,
Miyaguchi Hajime,
Kanamori Tatsuyuki,
Iwata Yuko T.,
Inoue Hiroyuki
Publication year - 2012
Publication title -
journal of forensic sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.715
H-Index - 96
eISSN - 1556-4029
pISSN - 0022-1198
DOI - 10.1111/j.1556-4029.2011.02039.x
Subject(s) - mdma , methamphetamine , pharmacology , stimulant , amphetamine , hallucinogen , ecstasy , metabolism , chemistry , designer drug , enzyme , in vivo , in vitro , cyp2d6 , cytochrome p450 , drug , biochemistry , medicine , biology , endocrinology , dopamine , microbiology and biotechnology , psychiatry
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.