Inhibition of capsaicin-induced cough by the gamma-aminobutyric acid agonist baclofen

Gamma-aminobutyric acid (GABA) is a central inhibitory neurotransmitter that also exists in the lungs. The GABA-agonist baclofen has been shown to have antitussive activity via a central mechanism in animals. Recently it was demonstrated that a 14-day course of baclofen given three times daily significantly inhibits the cough reflex in healthy volunteers. Because of the prolonged antitussive effect of baclofen that has been previously observed, the present study was conducted to evaluate the antitussive effect of low-dose, oral baclofen given once daily. Forty-one healthy volunteers were randomly assigned in a double-blind manner to receive a 28-day course of baclofen, either 10 mg or 20 mg once daily, or placebo. Subjects underwent cough challenge testing with inhaled capsaicin to establish baseline cough reflex sensitivity, and subsequently after 14 and 28 days of therapy. Subjects receiving baclofen 20 mg daily demonstrated significant inhibition of cough sensitivity after 14 days and after 28 days of therapy compared with baseline. Neither placebo nor baclofen 10 mg daily had a significant effect on cough sensitivity. No serious side effects were experienced by any study participant. These results confirm the recent observation that baclofen has significant antitussive activity in humans. Further, once-daily administration of a relatively low dose of baclofen is sufficient to achieve significant cough inhibition, although at least 14 to 28 days of therapy may be required to attain maximal antitussive effect. These results support further investigation of baclofen or other GABA-agonists as potential therapeutic agents for chronic, nonproductive cough.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				K. Chung Review Series: Chronic cough: Future directions in chronic cough: mechanisms and antitussives Chronic Respiratory Disease, August 1, 2007; 4(3): 159 - 165. [Abstract] [PDF]

				A H Morice, L McGarvey, I Pavord, and on behalf of the British Thoracic Society Cough Gu Recommendations for the management of cough in adults Thorax, September 1, 2006; 61(suppl_1): i1 - i24. [Full Text] [PDF]

				D. C. Bolser Cough Suppressant and Pharmacologic Protussive Therapy: ACCP Evidence-Based Clinical Practice Guidelines Chest, January 1, 2006; 129(1_suppl): 238S - 249S. [Abstract] [Full Text] [PDF]

				P. V. Dicpinigaitis and R. V. Alva Safety of Capsaicin Cough Challenge Testing Chest, July 1, 2005; 128(1): 196 - 202. [Abstract] [Full Text] [PDF]

				A.H. Morice and committee members The diagnosis and management of chronic cough Eur. Respir. J., September 1, 2004; 24(3): 481 - 492. [Full Text] [PDF]

				B. Bettler, K. Kaupmann, J. Mosbacher, and M. Gassmann Molecular Structure and Physiological Functions of GABAB Receptors Physiol Rev, July 1, 2004; 84(3): 835 - 867. [Abstract] [Full Text] [PDF]