INHIBITION OF CAPSAICIN-INDUCED COUGH BY THE GAMMA-AMINOBUTYRIC-ACID AGONIST BACLOFEN

gamma-aminobutyric acid (GABA) is a central inhibitory neurotransmitte r that also exists in the lungs. The GABA-agonist baclofen has been sh own to have antitussive activity via a central mechanism in animals. R ecently it was demonstrated that a 14-day course of baclofen given thr ee times daily significantly inhibits the cough reflex in healthy volu nteers. Because of the prolonged antitussive effect of baclofen that h as been previously observed, the present study was conducted to evalua te 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 wit h inhaled capsaicin 10 establish baseline cough reflex sensitivity, an d subsequently after 14 and 28 days of therapy. Subjects receiving bac lofen 20 mg daily demonstrated significant inhibition of cough sensiti vity 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 st udy participant. These results confirm the recent observation that bac lofen has significant antitussive activity in humans. Further, once-da ily administration of a relatively low dose of baclofen is sufficient to achieve significant cough inhibition, although at least 14 10 28 da ys of therapy may be required to attain maximal antitussive effect. Th ese results support further investigation of baclofen or other GABA-ag onists as potential therapeutic agents for chronic, nonproductive coug h. (C)1998 The American College of Clinical Pharmacology.