Centrally Mediated Inhibitory Effect of 5-[2-(Diethylamino)ethyl]amino-5, 11-dihydro[1]benzoxepino[3, 4-b]pyridine Trihydrochloride (KW-5805) on Gastric Acid Secretion in Rats

[摘要] References(25)Cited-By(6)KW-5805, 5-[2-(diethylamino)ethyl]amino-5, 11-dihydro[1]benzoxepino[3, 4-b]pyridine trihydrochloride, is a new tricyclic compound with antiulcer activities. Its effect on stimulated gastric acid secretion was investigated in the perfused stomach of anesthetized rats. KW-5805 at 0.3-10 mg/kg, i.v., dosedependently inhibited gastric acid secretion stimulated by 2-deoxy-D-glucose (2DG). On the other hand, the compound at 10-20 mg/kg, i.v., exerted a moderate decrease in gastric acid secretion stimulated by bethanechol; and at 10 mg/kg, i.v., it produced no change in gastric acid secretion evoked peripherally by vagal electrical stimulation. When applied intracerebroventricularly at 1-5 μg/rat, this compound dose-relatedly reduced gastric acid secretion stimulated by 2-DG. Three main metabolites (KF-10504, KF-9530 and KF-10847) of KW-5805 at 1 mg/kg, i.v., caused no significant decrease in gastric acid secretion stimulated by 2-DG. Doxepin, a tricyclic compound, definitely depressed the 2-DG stimulated gastric acid secretion at 1 mg/kg, i.v. It is suggested that intravenous administration of KW-5805 inhibits gastric acid secretion stimulated by 2-DG, mainly via centrally mediated mechanisms, and that biotransformation of KW-5805 to the metabolites contributes little to the development of the antisecretory effect.

[学科分类] 药理学