抄録
Biochemical and pharmacological properties of a newly synthesized compound, 2-[(2-dimethylaminobenzyl)sulfinyl] benzimidazole (NC-1300), were studied. NC-1300, at pH 6.0, potently inhibited the activity of H+K+ATPase in the rabbit gastric mucosa, thereby classifying it as a proton pump inhibitor. The inhibitory efficacy of NC-1300 on the pump was much the same as that seen with omeprazole. NC-1300 had no effect on acetylcholine-stimulated ileum contraction in guinea pigs at 10-5 M, but it non-competitively inhibited the contraction at 10-4 M. NC-1300 had no effect on histamine-stimulated atrial beating frequency in guinea pigs at 10-4 or 10-5 M. NC-1300, given either intraduodenally or orally, had a potent and long-lasting (more than 24 hr) inhibitory effect on gastric secretion in pylorus-ligated rats. Pretreatment with NC-1300 dose-dependently protected the gastric mucosa from damage induced by pylorus ligation, water-immersion stress, aspirin, and indomethacin, and the duodenal mucosa from damage induced by mepirizole in rats. We conclude that the antisecretory activity of NC-1300 appears to be mainly related to an inhibition of H+K+ATPase, while its anti-gastric and antiduodenal lesion activities are primarily related to an antisecretory effect.
