Effect of AS-2646, a novel antiulcer agent on gastric mucosal defensive factors in rats

The effects of AS-2646 on the acute gastric mucosal lesions induced by various noxious agents and the gastric mucosal defensive factors were studied in rats, and the following results were obtained: 1) AS-2646 (5-100 mg/kg, p.o.) dose-dependently inhibited the formation of the mucosal lesions induced by ethanol, ethanol-HCl, taurocholate-HCl and serotonin, and its anti-lesion spectrum was the widest among the compounds (cimetidine, pirenzepine, sulpiride and prostaglandin E1) examined here. 2) AS-2646 (5-10 mg/kg, p.o.) not only improved the changes of gastric mucosal hemodynamics induced by the blood removal and/or the reserpine treatment, but also inhibited the mucosal lesions induced by them. 3) AS-2646 (2-20 mg/kg, p.o.) antagonized the decrease in the surface gastric mucus and mucosal hexosamine contents induced by stress and/or aspirin. 4) AS-2646 (2-20 mg/kg, p.o.) caused no significant effect on the gastric mucosal prostaglandin E2 levels. 5) AS-2646 inhibited Campylobacter pylori in vitro. These results indicate that AS-2646 may be useful as a novel antiulcer drug with the defensive factor-potentiating and anti-Campylobacter pylori effects.