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 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 cytoprotective 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.
Kosaka
N
N
Department of Pharmacology, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
Tanaka
H
H
Tomaru
A
A
Ishii
A
A
Shuto
K
K
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001584:Benzoxepins / Q000494:pharmacology / Q000627:therapeutic use*; D002927:Cimetidine / Q000627:therapeutic use; D003864:Depression, Chemical; D004381:Duodenal Ulcer / Q000188:drug therapy*; D000431:Ethanol / Q000009:adverse effects; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006851:Hydrochloric Acid / Q000009:adverse effects; D008297:Male; D009336:Necrosis; D010890:Pirenzepine / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains; D013276:Stomach Ulcer / Q000188:drug therapy*; D013656:Taurocholic Acid / Q000009:adverse effects
D000897:Anti-Ulcer Agents; D001584:Benzoxepins; C055432:KW 5805; D010890:Pirenzepine; D000431:Ethanol; D013656:Taurocholic Acid; D002927:Cimetidine; D006851:Hydrochloric Acid