title: Biochemical and pharmacological analysis of 2-[(2-dimethylaminobenzyl)sulfinyl] benzimidazole (NC-1300), a new proton pump inhibitor.
abstract: 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 antigastric and antiduodenal lesion activities are primarily related to an antisecretory effect.
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000109:Acetylcholine / Q000494:pharmacology; D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors*; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001241:Aspirin / Q000633:toxicity; D001562:Benzimidazoles / Q000494:pharmacology*; D004386:Duodenum / Q000187:drug effects; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006168:Guinea Pigs; D017506:H(+)-K(+)-Exchanging ATPase; D006339:Heart Rate / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D007213:Indomethacin / Q000633:toxicity; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009853:Omeprazole; D010437:Peptic Ulcer / Q000517:prevention & control; D011817:Rabbits; D051381:Rats; D013312:Stress, Physiological / Q000473:pathology
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D001562:Benzimidazoles; C048733:2-((2-dimethylaminobenzyl)sulfinyl)benzimidazole; D006632:Histamine; D000251:Adenosine Triphosphatases; D017506:H(+)-K(+)-Exchanging ATPase; D009853:Omeprazole; D000109:Acetylcholine; D001241:Aspirin; D007213:Indomethacin