Pharmacology of harmalan (1-methyl-3,4-dihydro-beta-carboline)

Harmalan is presumably formed in vivo as an intermediate product of the biosynthesis of harman as well as tetrahydroharman. The pharmacological effects of harmalan as well as its affinity towards benzodiazepine, 5-HT2 and tryptamine binding sites were investigated in the present study. Harmalan induced clonic convulsions which were antagonized by diazepam. Receptor binding experiments as well as combined treatments with antagonists point to an interaction which involves neither benzodiazepine nor 5HT2 receptor sites but rather tryptamine binding sites. Good agreement was found between the potency of harmalan to increase spontaneous motor activity and the affinity to the tryptamine binding sites when compared with the effects of tryptamine in both tests. In the light-dark-chamber test for predicting anxiolytic effects of drugs, harmalan elicited opposite effects to diazepam. The results of combined treatment also suggested an interaction of both compounds not involving benzodiazepine receptors. Tryptamine binding sites seemed to play no role since the amine was inactive under these conditions. Thus, harmalan induces several tryptamine agonistic effects and others not involving tryptamine binding sites.