Effects of KW-5805, a New Antiulcer Agent, on Experimental Gastric and Duodenal Ulcers, Gastric Mucosal Lesions by Necrotizing Agents and Gastric Acid Secretion

• Published in: Japanese Journal of Pharmacology 1994, Vol.65(4), pp.305-312
• Main Authors: Kosaka, Nobuo, Tanaka, Hiroshi, Tomaru, Atsushi, Ishii, Akio, Shuto, Katsuichi
• Format: Article
• Language: English
• Subjects: Animals; Anti-Ulcer Agents - pharmacology; Anti-Ulcer Agents - therapeutic use; Antiulcer effect; Benzoxepins - pharmacology; Benzoxepins - therapeutic use; Biological and medical sciences; Cimetidine - therapeutic use; Cytoprotection; Depression, Chemical; Digestive system; Duodenal Ulcer - drug therapy; Ethanol - adverse effects; Gastric Acid - metabolism; Gastric acid secretion; Gastric Mucosa - drug effects; Gastric Mucosa - metabolism; Gastric Mucosa - pathology; Hydrochloric Acid - adverse effects; KW-5805; Male; Medical sciences; Necrosis; Pharmacology. Drug treatments; Pirenzepine - therapeutic use; Rats; Rats, Inbred Strains; Stomach Ulcer - drug therapy; Taurocholic Acid - adverse effects
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1254/jjp.65.305

Effects of KW-5805, a new antiulcer agent, on various experimental ulcers, necrotizing agent-induced gastric lesions and gastric acid secretion in rats were compared with those of pirenzepine and cimetidine. KW-5805 showed antiulcer activities against experimental gastric and duodenal ulcers (ED50 = 1.2-10.0 mg/kg, p.o.). KW-5805 effectively inhibited gastric lesions induced by various necrotizing agents (ED50=4.5-39.8 mg/kg, p.o.). In addition, the cytoprotecive effect of KW-5805 was not affected by indomethacin, but reserved by N-ethylmaleimide. These antiulcer and cytoprotective effects of KW-5805 were more potent than those of pirenzepine and cimetidine. In pylorus-ligated rats, intraduodenal KW-5805 administration at 30 mg/kg showed a weak antisecretory effect, which was 3-10 times less potent than those of pirenzepine and cimetidine. In rats with acute gastric fistula, intravenous injection of KW-5805 reduced methacholine-stimulated gastric acid secretion at doses of 10 and 30 mg/kg and inhibited tetragastrin-induced acid secretion at 30 mg/kg. These results indicate that KW-5805 has potent and broad antiulcer properties, which are probably exerted by its potent cytoprotective effect in addition to its antisecretory effect.