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

Male donryu rats (200-220 g) and mongrel dogs of both sexes (7-20 kg) were used. Histamine-induced ulcers: Histamine 2HCl (100 mg/kg) was given i.p. to 24 hr-fasted rats and the animals were killed 4 hr later. Histamine 2HCl in beeswax (20 mg/kg) was given i.m. to dogs once daily for 5 days and the animals were killed on the 6th day. Aspirin-induced ulcers: Aspirin (100 mg/kg) was given p.o. to the 24 hr-fasted rats and dogs twice (15 h apart) and the animals were killed 9 hr after the second administration of aspirin. Either the length (mm) or ares (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 about two times (in rats) or 9 times (in dogs) more potent than cimetidine. However, 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.