Agents with tricyclic structures for treating peptic ulcer disease.

The pathogenesis, clinical signs, and conventional treatment of peptic ulcer disease (PUD) are briefly discussed, and the use of drugs with tricyclic structures in the treatment of PUD is reviewed. Peptic ulcers occur most commonly in the duodenal bulb and the stomach. Numerous factors contribute to the formation of peptic ulcers, but an imbalance between acid and pepsin secretion and mucosal resistance is considered important. Conventional drug therapy of PUD with antacids, H2-receptor antagonists, anticholinergic drugs, and sucralfate is designed to correct this imbalance by neutralizing acid, inhibiting acid secretion, preventing contact of the ulcer with acid and pepsin, and enhancing mucosal defense mechanisms. Tricyclic agents that appear to be useful in the treatment of PUD are the tricyclic antidepressants, trimipramine maleate and doxepin hydrochloride, and the selective antimuscarinic drug, pirenzepine hydrochloride. The therapeutic effects of tricyclic antidepressants may result from their anticholinergic, antidepressant, and H2-receptor blocking actions. Controlled clinical trials suggest that trimipramine 50 mg/day (as the maleate salt) and pirenzepine hydrochloride 100-150 mg/day are superior to placebo and may be as effective as cimetidine for the short-term treatment of duodenal ulcers. Limited data suggest that these drugs are also effective for treating gastric ulcers. Assessment of the apparent efficacy of doxepin in duodenal ulcer treatment requires further study. Anticholinergic side effects and sedation associated with the administration of tricyclic agents may limit their usefulness as first-line anti-ulcer agents. With further evidence of their efficacy, trimipramine, doxepin, and pirenzepine may play an important role in the treatment of patients unresponsive to conventional anti-ulcer therapy.