Pharmacological properties of the reversible inhibitor of the gastric $H^+/K^+$ ATPase, AU-164

AU-164 was synthesized as a reversible gastric $H^+/K^+$ ATPase inhibitor, and its effects were tested in various systems. AU-164 inhibited rabbit gastric $H^+/K^+$ ATPase with an $IC_{50}$/ of 9 $\mu$M. On the other hand, AU-164 was a weak inhibitor for dog kidney $Na^+/K^+$ ATPasc, indicating the selectivity for gastric $H^+/K^+$ ATPase. The reversible property of the AU-164-induced inhibition of $H^+/K^+$ ATPase was confirmed by filtering the inhibition mixture through Sephadex G-25M column. In vivo basal acid secretion was also inhibited by AU-164 under the pylorus ligation of Sprague-Dawley rats. In addition, AU-164 protected dose dependently gastric lesion induced by ethanol in rats. The $ED_{50}$ value of 62 mg/kg p.o was estimated. These results suggest that AU-164 is a potent, selective and reversible gastric $H^+/K^+$ ATPase inhibitor, and that AU-164 has a potential use for the clinical therapeutics of peptic ulcer disease.