Misoprostol: discovery, development, and clinical applications

Misoprostol is a synthetic 15-deoxy-16-hydroxy-16-methyl analog of PGE1, and the first prostaglandin to be registered for the treatment of peptic ulcer disease. Misoprostol is a safe and well-tolerated drug that exerts potent gastric antisecretory effects and mucosal protective actions on the gastric and duodenal mucosa. In a dosage of 800 micrograms daily in two or four divided doses, misoprostol produced rates of complete ulcer healing in both gastric and duodenal ulcer patients significantly superior to placebo and comparable to H2 receptor antagonists. The major adverse effect is diarrhea in about 10% of patients, but this is usually mild and self-limiting. Misoprostol possesses uterotonic activity and should not be used in pregnant women or those who wish to become pregnant. Misoprostol effectively heals and prevents NSAID-induced gastropathy, a therapeutic need previously unserved. Due to its mucosal protective properties, misoprostol may have advantages over antisecretory drugs in the compromised patient who is a chronic smoker or alcohol user, in refractory duodenal ulcer patients, in recurrent ulcer, and in emergency use for acute upper GI bleeding. Misoprostol's tissue-protective effects may also extend to other therapeutic areas.