COMPARISON OF THE ANTITUSSIVE EFFECTS OF CODEINE AND THE GABA-AGONISTBACLOFEN

gamma-Aminobutyric acid (GABA) is an inhibitory transmitter of the cen tral 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 demonstrat ed the antitussive activity of a 14-day course of low-dose oral baclof en in normal subjects. In the present study, we evaluated a standard c ough suppressant, codeine, and compared its antitussive effect with th at 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), baclo fen (40mg) or placebo, which were dispensed in a randomised, double-bl ind manner. During each study, the concentration of capsaicin inducing 5 or more coughs (C-5) was determined. Significant suppression of cou gh was achieved by codeine (p = 0.021). Although a single dose of bacl ofen demonstrated cough suppression in some individuals, its effect wa s not significant for the study group as a whole (p = 0.066). The chan ge in cough threshold from baseline (Delta log C-5) produced by single doses of codeine and baclofen were not significantly different (p = 0 .434). In light of our previous study that demonstrated the significan t antitussive effect of a 14-day course of low-dose baclofen. the inab ility of a single, large dose of baclofen to suppress cough in the cur rent study suggests the need for multiple administrations to achieve t he optimal inhibitory effect of this agent.