The antisecretory effects of clozapine, a dopamine D4 receptor antagonist, are blocked by the dopamine D1 receptor antagonist, SCH23390.
Dopaminergic compounds affect gastric secretion and response to experimental gastric mucosal injury. We showed previously that the novel dopamine D4 receptor antagonist, clozapine, significantly reduces gastric acid secretion and restraint stress-induced gastric lesions. Because the selectivity of clozapine for D4 receptors has recently been questioned, we tested the ability of a known D1 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 D4 and D1 receptor, respectively, as previously believed.
Glavin
G B
GB
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
D000818:Animals; D000863:Antacids / Q000037:antagonists & inhibitors*; D001552:Benzazepines / Q000494:pharmacology*; D003024:Clozapine / Q000037:antagonists & inhibitors*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004347:Drug Interactions; D005744:Gastric Acid / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012636:Secretory Rate / Q000187:drug effects
D000863:Antacids; D001552:Benzazepines; D018492:Dopamine Antagonists; D003024:Clozapine