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Both KB-5492, a new anti-ulcer agent, and cimetidine, administered orally at 25-200 mg/kg, dose-dependently prevented cysteamine (400 mg/kg, s.c.)-induced duodenal ulcers in rats with ED50 values of 63 and 40 mg/kg, respectively. Anti-ulcer doses of cimetidine, but not KB-5492, inhibited gastric acid hypersecretion induced by cysteamine (400 mg/kg, s.c.). In contrast, anti-ulcer doses of KB-5492, but not cimetidine, increased duodenal HCO3- secretion in normal anesthetized rats. These findings suggest that KB-5492 prevents cysteamine-induced duodenal ulcers by stimulating duodenal HCO3- secretion, whereas cimetidine does so by inhibiting cysteamine-induced gastric acid hypersecretion.

japanese journal of pharmacology/japanese journal of pharmacology

4-Methoxyphenyl 4-(3,4,5-Trimethoxybenzyl)-1-Piperazineacetate Monofumarate Monohydrate (KB-5492), a New Anti-Ulcer Agent with a Selective Affinity for the Sigma Receptor, Prevents Cysteamine-Induced Duodenal Ulcers in Rats by a Mechanism Different from That of Cimetidine