Effects of azelastine hydrochloride, a new antiallergic drug, on the gastrointestinal tract.

Effects of 4-(p-chlorobenzyl)-2-(hexahydro-1-methyl-1H-azepin-4-yl)-(2H)-phthalazinone hydrochloride (azelastine hydrochloride), a new antiallergic drug, on the gastrointestinal tract were experimentally studied in comparison with diphenhydramine and clemastine. In the isolated guinea pig ileum, the dose-response curve for histamine was shifted to the right by 10(-8) mol/l of diphenhydramine, clemastine or azelastine to the same degree. Clemastine and azelastine reduced the maximum response in the dose-response curve, while diphenhydramine caused a parallel shift. In addition to the potent antihistamine action, azelastine at higher dose antagonized serotonin action and clemastine markedly inhibited the contractile responses of isolated intestinal preparations to acetylcholine and bradykinin. Azelastine and clemastine (50 mg/kg intraduodenally) reduced gastric secretion in pylorus ligated rats. Azelastine (5 mg/kg i.v.), clemastine (1 mg/kg i.v.) and diphenhydramine (1 mg/lg i.v.) depressed gastrointestinal motility in conscious rats. Biliary and pancreatic secretions of anesthetized rats were not affected by 1 mg/kg i.v. of azelastine or clemastine.