Gastric antisecretory activity of an acid stable H+/K+ ATPase inhibitor, WY-26,769

✍ Scribed by John F. DiJoseph; George J. Palumbo; Roger Crossley; Arthur A. Santilli; Susan T. Nielsen

• Publisher: John Wiley and Sons
• Year: 1991
• Tongue: English
• Weight: 406 KB
• Volume: 23
• Category: Article
• ISSN: 0272-4391
• DOI: 10.1002/ddr.430230106

✦ Synopsis

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 I C, , of 6.8 pM.

Wy-26,769 and its oxidative metabolite Wy-26,876 each inhibited the H+/K' ATPase (lC50 = 42 pM and 18 pM, respectively). In whole animal studies, Wy-26,769 inhibited histaminestimulated gastric acid secretion (IDso = 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.