Two metabolic pathways of tetrahydronorharmane (Tetrahydro-?-carboline) in rats

Abstract
Metabolites of (14C)tetrahydronorharmane (THN, tetrahydro-β-carboline) have been identified by mass spectrometry and nuclear magnetic resonance spectroscopy. Two metabolic pathways are suggested: Hydroxylation of the benzene ring — most probably with an epoxide as intermediate — though no hydroxylated THN could be detected in the urine samples of male and female rats but conjugated compounds as the main metabolites. The intermediary epoxide is supported by the fact, that the hydroxy substituent of THN is positioned on C-6 or C-7 with a ratio of 55:45 in female rats and of 45:55 in male rats. Dehydrogenation yielding norharmane. This substance possibly gives rise to another metabolite — 1,2-dihydro-β-carboline-1-one. The pharmacological and toxicological implications of these findings are discussed.

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