Effects of YJA20379-4 on gastric secretion, Helicobacter pylori growth and various gastric and duodenal lesions in rats.

Effects of a newly synthesized antiulcer agent, YJA20379-4, on gastric proton pump (H+/K+-ATPase) activity, Helicobacter pylori (H. pylori) growth, gastric acid secretion, and gastro-duodenal lesions, were examined in comparison with those of omeprazole. YJA20379-4 markedly inhibited the H+/K+-ATPase activity in a concentration-dependent manner and the inhibitory effect was increased under a weak acidic condition; the IC50 values were 32 and 81 microM at pH 6.4 and 7.4, respectively. The inhibition was completely antagonized by 0.5 mM dithiothreitol (DTT). In addition, YJA20379-4 showed a significant anti-H. pylori activity determined by the agar dilution method. The value of minimum inhibitory concentration (MIC, 3.9-11.7 microg/ml) was at least 3 times more potent than that of omeprazole. In pylorus ligated rats, YJA20379-4 inhibited basal gastric acid secretion when administered by the intraduodenal route (ED50: 23.6 mg/kg). In experimental ulcer models, YJA20379-4 administered by the oral route dose-dependently prevented the development of gastro-duodenal lesions in rats. Moreover, repeated administration of YJA20379-4 promoted the healing of gastric ulcers induced by acetic acid. On the basis of the data obtained, it is suggested that YJA20379-4 has a wide spectrum of antiulcer activities, and its mode of antiulcer actions is dependent on the inhibition of H+/K+-ATPase activity and H. pylori growth and the enhancement of a mucosal defense. Thus, YJA20379-4 might prove to be a beneficial therapy for gastritis and peptic ulcer diseases.