Airway inflammation and tachykinins: prospects for the development of tachykinin receptor antagonists

The tachykinins substance P and neurokinin A are contained within sensory airway nerves. Immune cells form an additional source of tachykinins in inflamed airways. Elevated levels of tachykinins have been recovered from the airways of patients with asthma and chronic obstructive pulmonary disease. Airway inflammation leads to an upregulation of tachykinin NK1 and NK2 receptors. Preclinical studies have indicated a role for the tachykinin NK1, NK2 and NK3 receptors in bronchoconstriction, airway hyperresponsiveness and airway inflammation caused by allergic and nonallergic stimuli. Compounds that are able to block two or three tachykinin receptors hold promise for the treatment of airways diseases such as asthma and/or chronic obstructive pulmonary disease. (C) 2001 Elsevier Science B.V. All rights reserved.