Stimulating and inhibitory effects of the dopamine “stabilizer” (?)-OSU6162 on dopamine D2 receptor function in vitro

摘要

The effect of (?)-OSU6162 on the incorporation of GTPgammaS35 in the membranes of hD2l-transfected CHO cells was investigated. In the absence of dopamine the compound exerted a slight but significant stimulating action, suggesting a weak partial agonism. In the presence of dopamine, low concentrations (10 to 100 nM) enhanced the stimulating action of dopamine. This enhancing effect was reversed by higher concentrations of (?)-OSU6162 in a complex biphasic manner. The dopamine-enhancing action is proposed to be mediated by binding to an allosteric site with high affinity and the inhibitory component by a low-affinity binding to the orthosteric site of the dopamine receptor.