Arne Elof Brändström

Structure—activity relationships of omeprazole analogues and their mechanism of action

Abstract Omeprazole represents a new class of gastric acid secretion inhibitors, the sulphinylbemimidazoles . Per Lindberg and colleagues describe this first example of a clinically useful anti-ulcer agent in this group whose mechanism involves highly specific inhibition of H + /K + -ATPase, the gastric proton pump. Omeprazole is activated only at low pH, as occurs in the parietal cell and is thus highly selective. The active intermediate formed, a sulphenamide, reacts with a mercapto group of H + /K + -ATPase to form a disulphide inhibitor complex. The quantity of this sulphenamide on the luminal side of the parietal cell is related to the H + /K + -ATPase inhibitory effect .