Comparison of the Antitussive Effects of Codeine and the GABA-Agonist Baclofen

Abstract

γ-Aminobutyric acid (GABA) is an inhibitory transmitter of the central nervous system 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. We have recently demonstrated the antitussive activity of a 14-day course of low-dose oral baclofen in normal subjects. In the present study, we evaluated a standard cough suppressant, codeine, and compared its antitussive effect with that of a single dose of baclofen. 10 healthy, adult volunteers who had previously participated in a study evaluating the antitussive effect of a 14-day course of baclofen, underwent capsaicin cough challenge on three occasions, 2 hours after the ingestion of codeine (30mg), baclofen (40mg) or placebo, which were dispensed in a randomised, double-blind manner. During each study, the concentration of capsaicin inducing 5 or more coughs (C5) was determined. Significant suppression of cough was achieved by codeine (p = 0.021). Although a single dose of baclofen demonstrated cough suppression in some individuals, its effect was not significant for the study group as a whole (p = 0.066). The change in cough threshold from baseline (Δlog C5) produced by single doses of codeine and baclofen were not significantly different (p = 0.434). In light of our previous study that demonstrated the significant antitussive effect of a 14-day course of low-dose baclofen, the inability of a single, large dose of baclofen to suppress cough in the current study suggests the need for multiple administrations to achieve the optimal inhibitory effect of this agent.