Woo T W, Chang M S, Chung Y K, Kim K B, Sohn S K, Kim S G, Choi W S
Pharmacology and Toxicology Laboratory, Research and Development Center, Yung-Jin Pharmaceutical Co., Ltd., Kyunggi-Do, Korea.
Biol Pharm Bull. 1998 May;21(5):449-55. doi: 10.1248/bpb.21.449.
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.
将一种新合成的抗溃疡药物YJA20379 - 4与奥美拉唑相比，研究了其对胃质子泵（H⁺/K⁺ - ATP酶）活性、幽门螺杆菌（H. pylori）生长、胃酸分泌及胃十二指肠损伤的影响。YJA20379 - 4以浓度依赖的方式显著抑制H⁺/K⁺ - ATP酶活性，且在弱酸性条件下抑制作用增强；在pH 6.4和7.4时，IC50值分别为32和81 microM。0.5 mM二硫苏糖醇（DTT）可完全拮抗该抑制作用。此外，通过琼脂稀释法测定，YJA20379 - 4显示出显著的抗幽门螺杆菌活性。最小抑菌浓度（MIC，3.9 - 11.7 microg/ml）的值比奥美拉唑至少强3倍。在幽门结扎的大鼠中，通过十二指肠途径给药时，YJA20379 - 4可抑制基础胃酸分泌（ED50：23.6 mg/kg）。在实验性溃疡模型中，口服YJA20379 - 4可剂量依赖性地预防大鼠胃十二指肠损伤的发生。此外，重复给予YJA20379 - 4可促进乙酸诱导的胃溃疡愈合。根据所得数据，提示YJA20379 - 4具有广泛的抗溃疡活性，其抗溃疡作用方式依赖于对H⁺/K⁺ - ATP酶活性和幽门螺杆菌生长的抑制以及黏膜防御的增强。因此，YJA20379 - 4可能被证明是治疗胃炎和消化性溃疡疾病的有益疗法。
