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.
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Authors | N Kosaka, H Tanaka, A Tomaru, A Ishii, K Shuto |
Journal | Japanese journal of pharmacology
(Jpn J Pharmacol)
Vol. 65
Issue 4
Pg. 305-12
(Aug 1994)
ISSN: 0021-5198 [Print] Japan |
PMID | 7990267
(Publication Type: Comparative Study, Journal Article)
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Chemical References |
- Anti-Ulcer Agents
- Benzoxepins
- KW 5805
- Pirenzepine
- Ethanol
- Taurocholic Acid
- Cimetidine
- Hydrochloric Acid
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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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