Okabe S
Nihon Yakurigaku Zasshi. 1986 Apr;87(4):351-60. doi: 10.1254/fpj.87.351.
This is a review article on newly developed antisecretory drugs which are now called proton pump inhibitors. Gastric H+ is secreted from the secretory membrane of parietal cells into the lumen of the stomach, using energy obtained by destructing ATP with H+, K+-ATPase (proton pump). Various substituted benzimidazoles such as timoprazole, picoprazole, omeprazole, or NC-1300 potently inhibits this proton pump at pH 6.0, thereby resulting in a strong inhibition of gastric H+ secretion. This inhibition of H+ secretion lasts for a long period, ie, 1-3 days after a single oral or intraduodenal administration, both in experimental animals and humans. This long lasting activity of these compounds appears to be due to their accumulation in the parietal cells because of their low pKa values (about 4.0). Proton pump inhibitors dose-dependently inhibit the development of various experimental ulcers and accelerate healing of chronic gastric ulcers in animals. Since these compounds also potently inhibit the development of HCl X ethanol or HCl X aspirin-induced gastric ulcers in animals, they are considered to have a cytoprotective activity. Some of the compounds (e.g., omeprazole) afforded a complete healing of peptic ulcers in man when it was given once daily for 2 to 4 weeks, without any adverse effects. Therefore, these proton pump inhibitors appear to be promising drugs for the treatment of peptic ulcer diseases.
这是一篇关于新开发的抗分泌药物（现称为质子泵抑制剂）的综述文章。胃中的氢离子（H⁺）通过H⁺，K⁺ -ATP酶（质子泵）破坏ATP所获得的能量，从壁细胞的分泌膜分泌到胃腔中。各种取代的苯并咪唑，如替莫拉唑、匹考拉唑、奥美拉唑或NC - 1300，在pH 6.0时能有效抑制这种质子泵，从而强烈抑制胃H⁺分泌。这种对H⁺分泌的抑制作用持续很长时间，即在实验动物和人类中，单次口服或十二指肠内给药后持续1 - 3天。这些化合物的这种长效活性似乎是由于它们的低pKa值（约4.0）使其在壁细胞中积累。质子泵抑制剂剂量依赖性地抑制各种实验性溃疡的形成，并加速动物慢性胃溃疡的愈合。由于这些化合物还能有效抑制动物中盐酸X乙醇或盐酸X阿司匹林诱导的胃溃疡的形成，它们被认为具有细胞保护活性。一些化合物（如奥美拉唑）在每天给药一次，持续2至4周时，能使人类消化性溃疡完全愈合，且无任何不良反应。因此，这些质子泵抑制剂似乎是治疗消化性溃疡疾病的有前景的药物。
