Monoamine oxidase inhibitors in South American hallucinogenic plants part 2: Constituents of orally-active Myristicaceous hallucinogens

Alkaloid constituents in Myristicaceous bark and leaf samples and in purportedly hallucinogenic preparations derived from Myristicaceous sources were qualitatively and quantitatively analyzed using TLC, GC, alkaloid precipitation tests and GC/MS. Fourteen of the 27 bark and leaf samples analyzed contained detectable amounts of alkaloids. The major bases were N,N-dimethyltryptamine (DMT) and/or 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT); much smaller amounts of tryptamine and/or N-methyltryptamine (NMT) were also usually present. β-Carbolines were not detected in the bark or leaf samples. Considerable variation in alkaloid profiles was found, extending to different collections of the same species. Fourteen of the 20 Virola samples contained alkaloids; none of the 6 Iryanthera species had detectable alkaloids. Osteophloem platyspermum contained an indolic base, identified as N-methyl-tryptophan methyl ester. Seven samples of an orally-ingested drug made from Virola spp. were analyzed. All except one contained substantial amounts of tryptamines; the types and proportions of tryptamines present varied greatly between samples. Samples of Yanomama snuff including various admixtures were analyzed and all components but one contained tryptamines. The drug samples having the highest concentrations of alkaloids contained 15–20 mgg dry wt while the Myristicaceous bark and leaf samples had much lower concentrations ranging from 0.04 to 0.25 mgg dry wt. β-Carbolines were detected as trace constituents in only two of the Myristicaceous drug samples. Four Myristicaceous paste samples were bioassayed in self-experiments. Two of the samples were devoid of detectable hallucinogenic or physiological activity, while some degree of oral activity was detected in two other samples. The activity of a number of tryptamine derivatives as monoamine oxidase inhibitors (MAOI) was investigated using an in vitro enzyme assay. Activity was measured using single compounds and mixtures of compounds and the results were compared to the activity of samples of orally-ingested Myristicaceous pastes. Tryptamine derivatives had significantly less MAOI activity than the activity of β-carboline derivatives measured in a previous study. Some structural correlations for MAOI activity were found for the tryptamine derivatives. Samples of orally-ingested Myristicaceous pastes were assayed for MAOI activity. The inhibition elicited by the paste samples was closely matched by mixtures of tryptamine standards having comparable proportions and concentrations. These observations indicate that the MAOI activity of the pastes is due mainly to the high concentrations of tryptamines; the traces of β-carbolines or non-nitrogenous inhibitors present probably do not contribute significantly to the total inhibition. Thus it appears unlikely that the oral activity of the Myristicaceous pastes is due to the potentiation of the tryptamines via inhibition of MAO by β-carbolines; some mechanism other than MAO inhibition must be sought to account for the oral hallucinogenic activity of the Myristicaceous pastes if they are, in fact, orally active.