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 (C5) 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 C5 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.