N, N-dimethyltryptamine forms oxygenated metabolites via CYP2D6 - an in vitro investigation.
Xenobiotica; the fate of foreign compounds in biological systems December 1, 2023 Emma Eckernäs, Alicia Macan-Schönleben, Moa Andresen-Bergström et al. 6 citations
The psychedelic compound DMT is metabolized primarily by monoamine oxidase A, but other pathways are poorly understood. This work investigated cytochrome P450 (CYP) enzymes in DMT metabolism by incubating DMT with recombinant human CYP enzymes and human liver microsomes, then analyzing metabolites with high-resolution mass spectrometry. DMT was rapidly metabolized by CYP2D6, while stable with all other tested CYP enzymes. Metabolism in human liver microsomes was reduced by harmine and SKF-525A but not quinidine, likely due to residual MAO-A activity. CYP2D6 incubations produced mono-, di-, and tri-oxygenated metabolites, probably from hydroxylation on the indole core. The findings may affect safety for ayahuasca use in slow CYP2D6 metabolizers or with CYP2D6 inhibitors.