Effects of NC-1300-B,A new benzimidazole derivative,on hog gastric H+, K+-ATPase,gastric acid secretion and HCl-ethanol-induced gastric lesions in rats |
| |
Authors: | Susumu Okabe Yasushi Akimoto Shinichi Yamasaki Hitoshi Nagai |
| |
Institution: | (1) Department of Applied Pharmacology, Kyoto Pharmaceutical University, Misasagi, Yamashina, 607 Kyoto, Japan |
| |
Abstract: | This study was designed to determine the effect of a newly synthesized benzimidazole derivative NC-1300-B on H+,K+ -ATPase (proton pump) in the hog gastric mucosa and on the basal gastric acid secretion and necrotizing agent-induced gastric lesions in rats. NC-1300-B inhibited the proton pump in a concentration-dependent manner and concentrations which inhibited the enzyme activity by 50% were 4.4×10–6 M at pH 6.0 and 3.1 ×10–5 M at pH 7.4. NC-1300-B administered orally or intraperitoneally 0.5 hr before ligating the pylorus inhibited the gastric acid secretion in a dose-dependent manner. The ED50 values (doses which inhibit acid output or lesion formation by 50%) for acid secretion were 11.5 and 11.0 mg/kg with oral and intraperitoneal administration, respectively. The antisecretory effect in a dose of 100 mg/kg persisted for up to 72 hr. NC-1300-B administered orally or intraperitoneally 0.5 hr before HCl-ethanol administration protected against damage of the gastric mucosa in a dose-dependent manner. The ED50 values for lesion formation were 13.3 and 23.0 mg/kg with oral and intraperitoneal administration, respectively. This protection with an oral dose of 100 mg/kg persisted for up to 72 hr. While pretreatment with 5 mg/kg of indomethacin given subcutaneously did not appreciably reverse the NC-1300-B protection, the pretreatment with 10 mg/kg of N-ethylmaleimide given subcutaneously potently reversed the NC-1300-B protection. NC-1300-B administered intragastrically at 30 mg/kg significantly inhibited the amplitude of gastric contraction for 50 min after intragastric administration. These effects of NC-1300-B on gastric secretion and lesion formation are much the same as those of the established proton pump inhibitor omeprazole, except for the short duration of the action of omeprazole (<24 hr). |
| |
Keywords: | NC-1300-B proton pump inhibitor gastric acid secretion gastric lesions gastric motility omeprazole gastroprotection |
本文献已被 SpringerLink 等数据库收录! |
|