Metabolic pathways of the psychotropic-carboline alkaloids, harmaline and harmine, by liquid chromatography/mass spectrometry and NMR spectroscopy

Abstract

The β-carboline alkaloids, harmaline and harmine, are present in hallucinogenic plants <i>Ayahuasca</i> and <i>Peganum harmala</i>, and in a variety of foods. In order to establish the metabolic pathway and bioactivities of endogenous and xenobiotic bioactive β-carbolines, high-performance liquid chromatography, coupled with mass spectrometry, was used to identify these metabolites in human liver microsomes (HLMs) <i>in vitro</i> and in rat urine and bile samples after oral administration of the alkaloids. Three metabolites of harmaline and two of harmine were found in the HLMs. Nine metabolites for harmaline and seven metabolites for harmine, from the rat urine and bile samples, were identified. Among them, four <i>in vivo</i> metabolites were isolated and fully characterised by NMR analysis. For the first time, harmaline is shown transforming to harmine by oxidative dehydrogenation in rat. Five metabolic pathways were therefore proposed, namely, oxidative dehydrogenation, 7-<i>O</i>-demethylation, hydroxylation, <i>O</i>-glucuronide conjugation and <i>O</i>-sulphate conjugation.