Mechanism of action of omeprazole.

The inhibitory effect of omeprazole on gastric acid secretion in vivo and in vitro is presented. In the gastric fistula dog omeprazole was found to be about 10 times more potent than cimetidine. When omeprazole was administered in vivo, the inhibition of acid secretory rates was found to correlate with the degree of inhibition of the gastric H+K+ATPase purified from the omeprazole treated animals. The inhibitory action of omeprazole was found to depend on acid induced transformation of omeprazole into an active inhibitor of the gastric H+K+ATPase, as no inhibition was obtained when omeprazole was incubated under neutral conditions with either the isolated gastric mucosal or the H+K+ATPase preparations. A model is proposed in which the inhibition of acid formation is mediated by an inhibitory compound generated form omeprazole within the acid compartment of the parietal cell.