title: Specificity of the substituted benzimidazole B 823-08: a prodrug for gastric proton pump inhibition.
abstract: Substituted benzimidazoles are potent inhibitors of the parietal cell proton pump, the H+/K+-ATPase. One member of this group, the sulfide B 823-08 (2-[(4-methoxy-3-methyl-2-pyridylmethyl)-thio]-5-trifluoromethyl-(1H)- benzimidazole) inhibits gastric acid secretion in various in vivo models, but fails to affect acid secretion in the isolated, lumen perfused mouse stomach. In contrast, the corresponding sulfoxide (B 823-10) is active under both in vivo and in vitro conditions. Since the sulfide is metabolically transformed to sulfoxide in vivo, the sulfide behaves as a prodrug of the sulfoxide. No effects of biological significance are found on organ functions which critically depend on Na+/K+-ATPase activity. This is in line with observations that the sulfoxide needs activation in an acidic environment, which constitutes the basis of its specificity for inhibiting stimulated parietal cells.
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D000818:Animals; D001646:Bile / Q000378:metabolism; D003864:Depression, Chemical; D004285:Dogs; D004573:Electrolytes / Q000652:urine; D004594:Electrophysiology; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007668:Kidney / Q000201:enzymology; D008297:Male; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013270:Stomach / Q000502:physiology; D013440:Sulfides / Q000378:metabolism
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D004573:Electrolytes; D013440:Sulfides; C049709:B 823-10; C049708:B 823-08; D000251:Adenosine Triphosphatases; D009853:Omeprazole