Nonlinear Pharmacokinetics of (±)3,4-Methylenedioxymethamphetamine (MDMA) and Its Pharmacodynamic Consequences in the Rat
Drug Metabolism and Disposition October 19, 2013 Marta Concheiro, Michael H. Baumann, Karl B. Scheidweiler et al. 32 citations
MDMA, an illicit drug with potential clinical use for PTSD and anxiety, shows nonlinear accumulation in male rats due to metabolic autoinhibition. After doses of 2.5, 5, and 10 mg/kg, MDMA and its metabolite MDA increased more than proportionally with dose, while other metabolites remained constant. Serotonin syndrome severity correlated with MDMA concentrations, and core temperature correlated with MDA concentrations, suggesting distinct mechanisms for behavioral and hyperthermic effects. At 2.5 mg/kg, MDMA Cmax was 164 ± 47.1 ng/ml, with HHMA and HMMA as major metabolites and less than 20% converted to MDA. These findings, given similarities to human pharmacokinetics, support using rat data at clinically relevant doses.