THE ANTISECRETORY EFFECTS OF CLOZAPINE, A DOPAMINE D-4 RECEPTOR ANTAGONIST, ARE BLOCKED BY THE DOPAMINE D-1 RECEPTOR ANTAGONIST, SCH23390

Dopaminergic compounds affect gastric secretion and response to experimental gastric mucosal injury. We showed previously that the novel dopamine D-4 receptor antagonist, clozapine, significantly reduces gastric acid secretion and restraint stress-induced gastric lesions. Because the selectivity of clozapine for D-4 receptors has recently been questioned, we tested the ability of a known D-1 receptor blocker, SCH23390, to affect clozapine-induced reduction in gastric acid secretion. SCH23390 given i.p. or i.c.v., at doses that did not affect gastric acid secretion, significantly blocked the anti-secretory effect of clozapine, administered either peripherally or centrally. These data suggest that neither clozapine nor SCH23390 exhibit as high a degree of selectivity for the dopamine D-4 and D-1 receptor, respectively, as previously believed.