Three drug classes have been used to inhibit H+/K+ ATPases. H2-receptor antagonists, like cimetidine (Tagamet), inhibit the signaling pathway that leads to activation of the ATPase. This type of inhibitor is effective in treating ulcers but does not prevent them from forming, and patients develop tolerance to them after about one week, leading to a 50% reduction in efficacy. Proton pump inhibitors (PPIs) were later developed, starting with Timoprazole in 1975. PPIs are acid-activated prodrugs that inhibit the hydrogen-potassium ATPase by binding covalently to active pumps. Current PPIs like Omeprazole have a short half-life of approximately 90 minutes. Acid pump antagonists (APAs) or potassium-competitive acid blockers (PCABs) are a third type of inhibitor that blocks acid secretion by binding to the K+ active site. APAs provide faster inhibition than PPIs since they do not require acid activation. Revaprazan was the first APA used clinically in east Asia, and other APAs are being developed since they appear to provide better acid control in clinical trials.