Human psychopharmacology
-
Human psychopharmacology · Jan 2010
Randomized Controlled Trial Clinical TrialEffect of metabolic blockade on the psychoactive effects of dextromethorphan.
Variation in the activity of cytochrome P450 2D6 (CYP2D6) affects the pharmacokinetics and effectiveness of dextromethorphan (DM), because it controls the production of dextrorphan, an active metabolite, with higher affinity for the NMDA receptor than the parent compound. This study examined whether pharmacological inhibition of CYP2D6 activity with quinidine would mimic the genetic mutation and thus also alter the psychoactive effects of DM. ⋯ Compared to DM alone, quinidine pre-treatment inhibited DM metabolism and changed its subjective effects, demonstrating that the psychoactive properties of DM are a function of drug metabolism. These results demonstrate the relationship between CYP2D6 activity, plasma drug levels, and psychoactive drug effects, and have implications for both the abuse liability and therapeutic utility of DM.