Effect of KW-5805 on gastric mucus changes induced by water immersion-restraint stress and aspirin in rats

The effects of 5-[2-(diethylamino)ethyl]amino-5, 11-dihydro[1]benzoxepino[3, 4-b]pyridine trihydrochloride (KW-5805) on the changes of gastric mucus induced by stress and aspirin were studied in rats. Water immersion-restraint stress time-dependently decreased the gastric adherent mucus content and induced gastric ulcers. Aspirin, administered orally at 200 mg/kg, reduced the gastric adherent mucus level and produced gastric erosions. The diminution of gastric mucus reached a maximum at 3 hr, and a gradual return to the non-treatment value was observed subsequently. Pretreatment with KW-5805, given orally at 3, 10 or 30 mg/kg, dose-dependently prevented stress- and aspirin-induced mucus depletion and gastric ulceration. Gastric mucus glycoprotein levels, indicated by the contents of hexose and hexosamine, were also decreased by aspirin. KW-5805 pretreatment (30 mg/kg, p.o.) significantly inhibited the diminution of mucus glycoproteins. KW-5805 also increased the gastric adherent mucus content and the amount of glycoproteins in normal rats. These results suggested that the stimulating effects of KW-5805 on the secretion and storage of gastric mucus may account for some of its antiulcer properties.