Picoprazole is a specific inhibitor of H+/K+-ATPase with IC50 of 3.1±0.4 μM. Picoprazole inhibits the H+/K+-ATPase activity in a concentration-dependent manner. The IC50 value is 3.1±0.4 μM. Picoprazole is a specific inhibitor of H+/K+-ATPase and binds to 100-kDa polypeptides of the enzyme, dose dependently inhibited opening of the Cl- conductance by Cu2+-o-phenanthroline, indicating that the Cl- conductance is part of the function of the H+/K+-ATPase. The inhibitory effect of the three benzimidazole derivatives Timoprazole, Picoprazole, and Omeprazole on histamine and dbcAMP stimulated 14C-aminopyrine accumulation (H+ secretion) has been studied in isolated and enriched guinea-pig parietal cells. All compounds tested inhibit H+ secretion in a concentration dependent manner with IC50 values of 8.5±1.9 μM for Timoprazole, 3.9±0.7 μM for Picoprazole, and 0.13±0.03 μM for Omeprazole.