Antitussive effect of the GABA-agonist baclofen

Background: gamma-Aminobutyric acid (GABA) is a central inhibitory neurotransmitter that also exists in peripheral tissues, including the lung. The GABA-agonist baclofen has been shown, in animal studies, to inhibit cough via a central mechanism, but has not been investigated in humans (to our knowledge). Study objective: To evaluate the antitussive effect of baclofen in normal human subjects. Design: Randomized, double-blind, placebo-controlled study. Setting: Academic medical center. Participants: Twenty healthy, adult volunteers. Interventions: Subjects underwent cough challenge with inhaled capsaicin before and after a 14-day course of baclofen, 10 mg three times daily, or placebo. Capsaicin cough threshold (C-5) was defined as the concentration of inhaled capsaicin inducing five or more coughs. Results: Subjects receiving baclofen (n = 10) demonstrated a significant elevation of capsaicin cough threshold compared with placebo subjects (n = 10). Mean Delta log C-5 after treatment was 0.48 +/- 0.19 (SEM) for the baclofen group, and -0.06 +/- 0.12 for the placebo group (p = 0.024). Six of 10 subjects receiving baclofen, but none of the 10 subjects receiving placebo, demonstrated a fourfold or greater increase in capsaicin cough threshold (p = 0.0054). Conclusion: The antitussive activity of low-dose, oral baclofen demonstrated in this study supports further investigation of this drug, or other GABA-agonists, for a potential therapeutic role in the treatment of pathologic cough.