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Interaction of 3,4-Methylenedioxymethamphetamine and Methamphetamine During Metabolism by In Vitro Human Metabolic Enzymes and in Rats

NCJ Number
241231
Journal
Journal of Forensic Sciences Volume: 57 Issue: 4 Dated: July 2012 Pages: 1008-1013
Author(s)
Kenji Kuwayama, Ph.D.; Kenji Tsujikawa, Ph.D.; Hajime Miyaguchi, Ph.D.; Tatsuyuki Kanamori, Ph.D.; Yuko T. Iwata, Ph.D.; Hiroyuki Inoue, Ph.D.
Date Published
July 2012
Length
6 pages
Annotation
Illicit amphetamine-type stimulant (ATS) tablets commonly contain one or more active ingredients, which have hallucinogenic and/or stimulant effects.
Abstract
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, the researchers 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. Abstract published by arrangement with John Wiley & Sons.