Discussion of the Fate and Metabolism of Some Hallucinogenic Indolealkylamines

Abstract

This chapter explores the mechanism of action of hallucinogenic indolealkylamines, the study of their metabolism, and their interaction with 5-HT metabolism. Studies have shown that simple N -alkylated derivatives of tryptamine (DMT, DET and dipropyltryptamine (DPT)) are hallucinogenic in man. These compounds are metabolized through 6-hydroxylation, dealkylation, and deamination to form the corresponding intermediates. In rodents, 6-hydroxylation is a major pathway, but in man, it is a minor one. It is suggested that 6-hydroxylation might be a pathway to form psychotropically active metabolites, but 6-OHDMT—one of the metabolites of DMT—has been shown to be practically inactive in man. However, if 6-hydroxylation is prevented by substituting a fluoro atom in the 6-position of the indole ring, the resulting compound (6-FDET) is not hallucinogenic. Also, psilocin, the 4-OHDMT, is also a better (2–3 times as good) substrate for the dealkylating enzyme than 6-OHDMT. This compound is distinctly different from the other hallucinogenic indolealkylamines because it produces tremors at a much smaller dose level than DMT does. A more selective, quantitative, regional method which could measure drug effects in vivo would be more helpful in finding a specific metabolic test for hallucinogenic activity.