Targeting tachykinins for the treatment of obstructive airways disease

The tachykinin family of peptides are distributed throughout the nervous system and are thought to play a critical role in inflammation and immunomodulation. Tachykinins have been implicated in the pathogenesis of many diseases and disease processes including inflammatory pain, emesis, depression, Parkinson's disease and inflammatory bowel syndrome. In the airways of animals, substance P and neurokinin A are released from a subset of airway sensory nerves, and evoke vasodilatation, bronchoconstriction, mucus secretion, leukocyte recruitment, airways hyperreactivity and cough. These observations have led to suggestions that tachykinins may also be viable targets for the treatment of obstructive airways disease. Clinical trials in humans assessing the utility of tachykinin receptor antagonists such as nepadutant and saredutant for the treatment of asthma are limited, and the results for the most part have been inconclusive. Several new tachykinin receptor antagonists have been recently designed to target multiple tachykinin receptor subtypes and to readily penetrate into the central nervous system. Future clinical trials with these compounds should help to shed some light on the role of tachykinins in obstructive airways disease.