Effect of 5-[2-(diethylamino)ethyl]amino-5, 11-dihydro[1]benzoxepino[3, 4-b]pyridine trihydrochloride (KW-5805) on the biosynthesis of rat gastric mucus

Abstract

The effect of 5-[2-(diethylamino)ethyl]amino-5, 11-dihydro[1]benzoxepino[3, 4-b]pyridine trihydrochloride (KW-5805) on the activity of an enzyme regulating gastric mucous aminosugar metabolism was studied in rats. Restraint and water-immersion stress decreased the gastric mucosal glucosamine synthetase activity and induced gastric ulcers. The decrease of the enzyme activity reached a maximum at 1 hr and then returned to the non-stressed value. Pretreatment with KW-5805 at oral doses of 3 and 30 mg/kg inhibited the decrease of the enzyme activity and the gastric adherent mucus content and gastric ulceration induced by the stress. KW-5805 (30 mg/kg, p.o.) increased the enzyme activity in normal rats and also prevented the decrease of gastric mucosal N-acethylglucosamine kinase activity in the stressed rats. KW-5805 stimulated the activities of gastric mucosal UDP-N-acethylglucosamine 4-epimerase and UDP-galactosyltransferase in vitro. These results suggested that the antiulcerogenic effect of KW-5805 might be due to the activation of an enzyme regulating the biosynthesis of gastric mucus resulting in the reinforcement of gastric mucosal defensive mechanisms.