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.
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.
Morimoto
Y
Y
Department of Pharmacology, Kanebo, Ltd., Osaka, Japan.
Shimohara
K
K
Tanaka
K
K
Hara
H
H
Sukamoto
T
T
D000818:Animals; D000897:Anti-Ulcer Agents / Q000378:metabolism / Q000627:therapeutic use*; D001639:Bicarbonates / Q000378:metabolism; D002927:Cimetidine / Q000627:therapeutic use*; D003543:Cysteamine; D004381:Duodenal Ulcer / Q000139:chemically induced / Q000517:prevention & control*; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism; D005744:Gastric Acid / Q000378:metabolism; D007419:Intestinal Secretions / Q000187:drug effects; D008297:Male; D010879:Piperazines / Q000378:metabolism / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017480:Receptors, sigma / Q000187:drug effects / Q000378:metabolism*
D000897:Anti-Ulcer Agents; D001639:Bicarbonates; D010879:Piperazines; D017480:Receptors, sigma; C065167:KB 5492; D003543:Cysteamine; D002927:Cimetidine