Effects of monoamine oxidase inhibitor and cytochrome P450 2D6 status on 5-methoxy-N,N-dimethyltryptamine metabolism and pharmacokinetics.
Biochemical pharmacology July 1, 2010 Hong-Wu Shen, Chao Wu, Xi-Ling Jiang et al. 40 citations
The metabolism and pharmacokinetics of the natural psychoactive compound 5-MeO-DMT are strongly influenced by both CYP2D6 genetic variation and monoamine oxidase inhibitors (MAOIs). Compared to the wild-type CYP2D6.1 enzyme, the CYP2D6.2 variant showed 2.6-fold lower catalytic efficiency and CYP2D6.10 showed 40-fold lower efficiency in producing the active metabolite bufotenine. In human liver microsomes treated with the MAOI pargyline, 5-MeO-DMT O-demethylation correlated strongly with CYP2D6 activity. In mice with the human CYP2D6 gene, systemic exposure to bufotenine was 60% higher than in wild-type mice. Pretreatment with the MAOI harmaline increased systemic exposure to 5-MeO-DMT by 3.6- to 4.4-fold and to bufotenine by 6.1- to 9.9-fold, depending on mouse genotype. MAOIs substantially alter 5-MeO-DMT processing and bufotenine formation, with CYP2D6 genotype determining the extent of these effects.