Antidopaminergic effects of bisbenzyl and benzyl tetrahydroisoquinoline alkaloids.

Several bisbenzyl and benzyl tetrahydroisoquinoline (THIQ) alkaloids and bulbocapnine were examined for their abilities to displace 3H-spiperone binding from rat striatal membranes and to antagonize apomorphine-induced rotation in mice with unilateral striatal 6-hydroxydopamine lesions. Receptor binding study showed that bulbocapnine, bisbenzyl and benzyl THIQs exhibited an affinity for dopamine receptors spanning a seven-fold range. In lesioned mice, dauricine, several benzyl THIQs and THIQs antagonized apomorphine-induced rotation. The order of potencies in this test was: dauricine greater than hydrastinine greater than M-9260 greater than demethylcoclaurine, bulbocapnine much greater than cycleanine. In this test, the order of potency did not parallel that in the dopamine receptor binding test. These results suggest that dauricine, THIQs and several benzyl THIQ alkaloids have dopamine receptor blocking activity.