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Effects of KW-5805, a new antiulcer agent, on experimental gastric and duodenal ulcers, gastric mucosal lesions by necrotizing agents and gastric acid secretion.

Abstract
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.
AuthorsN Kosaka, H Tanaka, A Tomaru, A Ishii, K Shuto
JournalJapanese journal of pharmacology (Jpn J Pharmacol) Vol. 65 Issue 4 Pg. 305-12 (Aug 1994) ISSN: 0021-5198 [Print] Japan
PMID7990267 (Publication Type: Comparative Study, Journal Article)
Chemical References
  • Anti-Ulcer Agents
  • Benzoxepins
  • KW 5805
  • Pirenzepine
  • Ethanol
  • Taurocholic Acid
  • Cimetidine
  • Hydrochloric Acid
Topics
  • Animals
  • Anti-Ulcer Agents (pharmacology, therapeutic use)
  • Benzoxepins (pharmacology, therapeutic use)
  • Cimetidine (therapeutic use)
  • Depression, Chemical
  • Duodenal Ulcer (drug therapy)
  • Ethanol (adverse effects)
  • Gastric Acid (metabolism)
  • Gastric Mucosa (drug effects, metabolism, pathology)
  • Hydrochloric Acid (adverse effects)
  • Male
  • Necrosis
  • Pirenzepine (therapeutic use)
  • Rats
  • Rats, Inbred Strains
  • Stomach Ulcer (drug therapy)
  • Taurocholic Acid (adverse effects)

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