GASTRIC ANTISECRETORY ACTIVITY OF AN ACID STABLE H+/K+ ATPASE INHIBITOR, WY-26,769

Wy-26,769 (2-3-dihydro-2-(2-pyridinyl) thiazolo-[3,2-a]benzimidazole) is a gastric antisecretory agent that acts by inhibiting the parietal cell proton pump. In vitro, Wy-26,769 was active against dbcAMP-stimulated aminopyrine uptake in isolated parietal cells. Preincubating the drug with liver microsomal enzymes increased its potency 50 times, to an IC50 of 6.8-mu-M. Wy-26,769 and its oxidative metabolite Wy-26,876 each inhibited the H+/K+ ATPase (IC50 = 42-mu-M and 18-mu-M, respectively). In whole animal studies, Wy-26,769 inhibited histamine-stimulated gastric acid secretion (ID50 = 3 mg/kg) irrespective of whether Wy-26,769 was administered orally or intravenously. Wy-26,769 was not degraded in acid and also inhibited gastric acid secretion in the pylorus-ligated rat. Wy-26,769 was equiactive after oral or intravenous administration demonstrating that it is an acid stable proton pump inhibitor.