Developing antitussives the clinician's pipeline-what do we need?

The evolving concept of cough hypersensitivity, an over activity of the afferent sensory nerves in the upper airways, has given new insights into the pathophysiology underlying chronic cough. Armed with this new information drug development aimed at reducing cough reflex sensitivity to normal has, for the first time, led to successful clinical studies. This review outlines the concepts underlying the inflammatory processes leading to cough hypersensitivity and demonstrates how knowledge of the molecular pharmacology of hypersensitivity provides a lead into drug targets. Initial hope that antagonists of TRP receptors would reduce clinical cough has been disappointing. Drugs such as theobromine, thalidomide and AF 219 which all have activity on afferent sensory nerves have shown promise in clinical trials. Large-scale phase three clinical studies are required to confirm these exciting findings.