Gastroprotective agents for the prevention of NSAID-induced gastropathy.

Over 30 million people in the world take non-steroidal anti-inflammatory drugs (NSAID's). A large percentage of these individuals will develop gastric ulcers and related complications, a condition known as "NSAID gastropathy". NSAID gastropathy differs from classic peptic ulcer disease in many ways, and traditional peptic ulcer therapy is largely ineffective in preventing NSAID-induced gastropathy. The prostaglandin misoprostol has been shown to be effective and is approved for the prevention of NSAID gastropathy. However, misoprostol has side effects that limit its general use. For this reason, considerable effort throughout the 1990's has focused on the identification of new gastroprotective molecules. Some synthetic studies have been aimed at the preparation of new prostaglandins, prostacyclin mimetics, and thromboxane antagonists. New histamine H2 receptor antagonists have also been developed which, unlike cimetidine or ranitidine, now appear to couple true gastroprotective activity with antisecretory properties. One new H2 antagonist, ebrotidine, has shown clinical utility in preventing NSAID gastropathy. Many other types of structures (flavonoids, peptides, terpenoids, xanthines, others), as well as compounds displaying certain pharmacological actions (5-hydroxytryptamine receptor binding, adrenergic receptor binding, mast cell stabilization, others) have been linked in some way to gastroprotection. This article reviews many of these recent gastroprotection findings, with emphasis on those of potential use for prevention of NSAID gastropathy.