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 dr ug used at rave parties. Unfortunately, MDMA may have neurological effects and in some cases causes hepatotoxicity. MDMA binds to cytochrome P450 in r at and human hepatic microsomal preparations. Upon metabolic transformation of either the methylenedioxy or the methylamino function, it forms an inhi bitory P450-metabolite complex. This inhibitory complex is formed predomina ntly 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. (C) 1999 Elsevier Science B.V. All rights reserved.