Publication
Title
N, N-dimethyltryptamine forms oxygenated metabolites via CYP2D6-an in vitro investigation
Author
Abstract
  1. N, N-dimethyltryptamine (DMT) is a psychedelic compound that has shown potential in the treatment of depression. Aside from the primary role of monoamine oxidase A (MAO-A) in DMT metabolism, the metabolic pathways are poorly understood. Increasing this understanding is an essential aspect of ensuring safe and efficacious use of DMT.
  2. This work aimed to investigate the cytochrome 450 (CYP) mediated metabolism of DMT by incubating DMT with recombinant human CYP enzymes and human liver microsomes (HLM) followed by analysis using high-resolution mass spectrometry for metabolite identification.DMT was rapidly metabolised by CYP2D6, while stable with all other investigated CYP enzymes. The metabolism of DMT in HLM was reduced after inclusion of harmine and SKF-525A whereas quinidine did not affect the metabolic rate, likely due to MAO-A residues present in HLM. Analysis of the CYP2D6 incubates showed formation of mono-, di- and tri-oxygenated metabolites, likely as a result of hydroxylation on the indole core.
  3. More research is needed to investigate the role of this metabolic pathway in vivo and any pharmacological activity of the proposed metabolites. Our findings may impact on safety issues following intake of ayahuasca in slow CYP2D6 metabolizers or with concomitant use of CYP2D6 inhibitors.
Language
English
Source (journal)
Xenobiotica : the fate of foreign compounds in biological systems. - London, 1971, currens
Publication
Abingdon : Taylor & francis ltd , 2023
ISSN
0049-8254 [print]
1366-5928 [online]
DOI
10.1080/00498254.2023.2278488
Volume/pages
53 :8-9 (2023) , p. 515-522
ISI
001100707400001
Pubmed ID
37916667
Full text (Publisher's DOI)
Full text (open access)
UAntwerpen
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identifier
Creation 04.12.2023
Last edited 08.01.2024
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