Pharmacokinetics and pharmacodynamics of 3,4-methylenedioxymethamphetamine (MDMA): interindividual differences due to polymorphisms and drug–drug interactions
Critical Reviews in Toxicology October 3, 2012 Saskia J. Rietjens, Laura Hondebrink, Remco H S Westerink et al. 51 citations
The clinical outcome after MDMA intake ranges from mild entactogenic effects to life-threatening intoxication, and the most relevant mechanisms causing acute adverse effects remain unclear. Genetic factors, such as polymorphisms in CYP2D6 causing poor metabolism, and interactions from polydrug use, like co-exposure with selective serotonin reuptake inhibitors (SSRIs), modulate MDMA pharmacokinetics and dynamics. While SSRIs can increase MDMA plasma levels, they can reduce clinical effects like blood pressure and body temperature, possibly via pharmacodynamic interaction at the serotonin reuptake transporter. Pretreatment with inhibitors of dopamine or norepinephrine transporters, or antagonists like carvedilol, ketanserin, and haloperidol, can reduce multiple MDMA-induced effects. Investigating these drugs for treating MDMA intoxication is worthwhile.