Elsevier

Biological Psychiatry

Volume 28, Issue 10, 15 November 1990, Pages 841-848
Biological Psychiatry

Article
Observations on the metabolism of the psychotomimetic indolealkylamines: Implications for future clinical studies

https://doi.org/10.1016/0006-3223(90)90566-KGet rights and content

Abstract

Although the psychotomimetic indolealkyalmine N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, and 5-hydroxy-N,N-dimethyltryptamine have been unequivocally identified in human body fluids, evidence relating their concentration to the presence of psychotic illness in humans remains controversial. A series of studies on the metabolism of the compounds in the rat have highlighted the rapidity and with which these are metabolized and renally excreted. The implications of our observation for the interpretation of past clinical studies and the design of future ones is discussed.

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    In addition, blockage of MAO-mediated deamination metabolism of 5-MeO-DMT may cause variation in other metabolic pathways. The prior treatment of MAOI iproniazid or pargyline has been shown to redirect the metabolism of 5-MeO-DMT, resulting in higher levels of other metabolites in rat urine [32,33]. Compared with 5-MeO-DMT alone, co-incubation of 5-MeO-DMT with harmaline sharply increased the production of active metabolite bufotenine in human CYP2D6 EM hepatocytes (Fig. 2).

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Supported in part by the National Health and Medical Research Council of Australia.

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