Tetrahydroprotoberberine--a new chemical type of antagonist of dopamine receptors.

Abstract

In rats lesioned by unilateral micro-injection of 6-OHDA into substantia nigra, the apomorphine-induced contralateral rotation and the amphetamine-induced ipsilateral rotation were antagonized by THB, l-THP and haloperidol. Scopolamine reversed the antagonistic effect of THB against amphetamine. Thus, THB and l-THP exhibited the DA-receptor antagonistic property which was similar to that of haloperidol. l-SPD (10 mg/kg), however, only antagonized the amphetamine-challenged rotational response, while it could not antagonize, but potentiate, the apomorphine-challenged rotational response. So, l-SPD might be a partial agonistic antagonist of DA-receptors, and its effect was more potent than that of THB and l-THP. l-SPD would be ascertained further in clinic trial. From these results and others, the authors suggest that THPB is a new chemical type of antagonist of brain DA-receptors.