EFFECTS OF KW-5805, A NEW ANTIULCER AGENT, ON EXPERIMENTAL GASTRIC AND DUODENAL-ULCERS, GASTRIC-MUCOSAL LESIONS BY NECROTIZING AGENTS AND GASTRIC-ACID SECRETION

Effects of KW-5805, a new antiulcer agent, on various experimental ulc ers, necrotizing agent-induced gastric lesions and gastric acid secret ion in rats were compared with those of pirenzepine and cimetidine. KW -5805 showed antiulcer activities against experimental gastric and duo denal ulcers (ED(50) =1.2-10.0 mg/kg, p.o.). KW-5805 effectively inhib ited gastric lesions induced by various necrotizing agents (ED(50)=4.5 -39.8mg/kg, p.o.). In addition, the cytoprotecive effect of KW-5805 wa s not affected by indomethacin, but reserved by N-ethylmaleimide. Thes e antiulcer and cytoprotective effects of KW-5805 were more potent tha n those of pirenzepine and cimetidine. In pylorus-ligated rats, intrad uodenal 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 inject ion of KW-5805 reduced methacholine-stimulated gastric acid secretion at doses of 10 and 30 mg/kg and inhibited tetragastrin-induced acid se cretion at 30 mg/kg. These results indicate that KW-5805 has potent an d broad antiulcer properties, which are probably exerted by its potent cytoprotective effect in addition to its antisecretory effect.