Effect of an H+, K+-ATPase inhibitor, omeprazole (OPZ), on gastric acid secretion and gastric or duodenal lesion. Comparison with an H2-receptor antagonist, famotidine (FMD)

In pylorus ligated rats, OPZ inhibited gastric acid secretion dose-dependently, with a potency greater than that of FMD. At the same time, OPZ increased gastric K+ secretion and inhibited pepsin and Na+ secretions at the highest dose. In Heidenhain pouch dogs, single injection of OPZ inhibited gastric acid secretion induced by histamine to a degree almost equal to that by FMD. In the case of repeated administration, anti-secretory activity of OPZ was enhanced by up to several days and then remained constant. After several days, the inhibitory activity of OPZ was more potent and longer than that of FMD, and it still had not ceased 22hr after administration. In pylorus ligated rats, OPZ prevented gastric ulceration, and the potency was greater than that of FMD. OPZ promoted healing of gastric and duodenal ulcers induced by acetic acid in rats. At the same doses, FMD failed to promote the healing of both ulcers. In water-immersion stressed rats, OPZ prevented formation of gastric erosions, with a potency greater than that of FMD. In addition, OPZ prevented formation of gastric erosions induced by ethanol in rats. These results indicate that the anti-secretory and anti-ulcer activities of OPZ are superior to those of FMD, so that OPZ should have excellent therapeutic application for peptic ulcers.