Combined tachykinin receptor antagonists for the treatment of respiratory diseases

Abstract

The tachykinins, substance P (SP) and neurokinin A (NK-A), are thought to be key players in the process of neurogenic inflammation, which is believed to contribute to the pathogenesis of various respiratory diseases. Due to the additive nature of the respiratory effects of these sensory neuropeptides, inhibiting the effects of tachykinins at both NK₁ and NK₂ receptors may represent a therapeutic advantage for the treatment of asthma, as opposed to receptor-selective antagonists, which have demonstrated only minimal efficacy to date. A number of companies are pursuing small molecule approaches yielding compounds with potent, balanced NK₁ and NK₂ receptor antagonist activities. In allergic rhinitis, NK₁receptor antagonism may complement the actions of antihistamines by addressing nasal congestion, which is largely unrelieved by these otherwise highly efficacious agents. Novel combined H₁/NK₁ receptor antagonists have been developed and may represent a therapeutic option for the treatment of this disease.

• antihistamines
• asthma
• dual antagonists
• neurogenic inflammation
• rhinitis
• tachykinin antagonists