Nitric oxide in the gastrointestinal tract: opportunities for drug development

Nitric oxide (NO) plays important roles in gastrointestinal mucosal defence, as well as in the pathogenesis of several gastrointestinal diseases (e.g. irritable bowel syndrome and inflammatory bowel disease). The potent cytoprotective effects of NO have been demonstrated in a range of animal models. However, in some disease states, inhibition of NO synthesis is beneficial. Several attempts have been made to develop drugs for ulcerative and/or inflammatory disorders of the gastrointestinal tract, with varying degrees of success. Covalently linking a NO-releasing group to non-steroidal anti-inflammatory drugs or to drugs used in the treatment of inflammatory bowel disease and irritable bowel syndrome has shown some benefit, although no drug of this type has yet been fully developed.