Psychedelic 5-methoxy-N,N-dimethyltryptamine: metabolism, pharmacokinetics, drug interactions, and pharmacological actions.

摘要: 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) belongs to a group of naturally-occurring psychoactive indolealkylamine drugs. It acts as nonselective serotonin (5-HT) agonist and causes many physiological behavioral changes. 5-MeO-DMT is O-demethylated by polymorphic cytochrome P450 2D6 (CYP2D6) an active metabolite, bufotenine, while it mainly inactivated through the deamination pathway mediated monoamine oxidase A (MAO-A). often used with MAO-A inhibitors such harmaline. Concurrent use harmaline reduces metabolism leads prolonged increased exposure parent drug 5-MeO-DMT, well metabolite bufotenine. Harmaline, bufotenine act agonistically on serotonergic systems may result in hyperserotonergic effects or toxicity. Interestingly, CYP2D6 also has important contribution metabolism, genetic polymorphism cause considerable variability pharmacokinetics dynamics its interaction 5-MeO-DMT. Therefore, this review summarizes recent findings biotransformation, pharmacokinetics, pharmacological actions In addition, pharmacokinetic pharmacodynamic drug-drug interactions between potential involvement pharmacogenetics, risks intoxication are discussed.