Inhibitory metabolite complex formation of methylenedioxymethamphetamine with rat and human cytochrome P450. Particular involvement of CYP 2D.

Methylenedioxymethamphetamine (MDMA or ecstasy) is a common recreational drug used at rave parties. Unfortunately, MDMA may have neurological effects and in some cases causes hepatotoxicity. MDMA binds to cytochrome P450 in rat and human hepatic microsomal preparations. Upon metabolic transformation of either the methylenedioxy or the methylamino function, it forms an inhibitory P450-metabolite complex. This inhibitory complex is formed predominantly with the P450 2D isozymes. This complex formation may account for the clinical toxicity observed upon ingestion of MDMA, particularly with other compounds normally metabolized by P450 2D6.