Future opportunities for drug therapy in peptic ulcer disease.

Attempts to develop antisecretory agents showing a significant increase in potency and duration of action over currently available H2 antagonists have had to contend with the problem of gastric tumour induction during long-term toxicity testing in rats, and their clinical future is currently uncertain. A number of potential pharmacological approaches to ulcer therapy, unrelated to inhibition of acid secretion, can be identified upon which to base the search for new antiulcer drugs. Whether such agents are a commercially attractive proposition is debatable, given the disappointing early clinical experience with prostaglandins in acute healing studies together with the established efficacy and safety of cimetidine and ranitidine. Indeed it is difficult to foresee any agent challenging the dominance of H2 blockers during this century. By analogy with beta adrenoceptor antagonists, it is likely that new developments will take the form of some additions to the H2 range, improved formulations, additional indications, and possibly combination therapies with other drugs. Future research must address the different aetiologies of gastric and duodenal ulcer and other acid-peptic conditions as well as attempting to cure the disease rather than simply heal the ulcer. Advances in fields traditionally unrelated to peptic ulcer research such as growth regulation, vascular disorders, and inflammation may well provide the most profitable basis for longer-term drug research. Finally, animal toxicity studies with second generation antisecretory agents have inadvertently focused attention on gastric cancer, a disease where the need for new drugs is unquestionable.