Effects of ranitidine, a new histamine H2-receptor antagonist, on histamine- and aspirin-induced gastric ulcers in rats and dogs

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Abstract
Male Donryu rats (200-220 g) and mongrel dogs of both sexes (7-20 kg) were used. Histamine dehydrochloride (100 mg/kg) was given i.p. to 24 h-fasted rats and the animals were killed 4 h later. Histamine dehydrochloride in beeswax (10 mg/kg) was given i.m. to dogs once daily for 5 days and the animals were killed on the 6th day. Aspirin (100 mg/kg) was given orally to the 24 h-fasted rats and dogs twice (15 h apart) and the animals were killed 9 h after the 2nd administration. Either the length (mm) or area (mm2) of each ulcer was measured, summed and used as an ulcer index. Cimetidine and gefarnate were used as reference drugs. Ranitidine dose-dependently inhibited both histamine- and aspirin-induced ulcers in rats and dogs. On the basis of ED50, the antiulcer effect of ranitidine on histamine-induced ulcers was .apprx. 2 times (in rats) or 9 times (in dogs) more potent than cimetidine. The antiulcer effect of ranitidine on aspirin-induced ulcers was 1.7 times more potent than cimetidine (in rats) or almost equal (in dogs) to cimetidine. Gefarnate had an insignificant effect on both histamine- and aspirin-induced ulcers.

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