Negative effect of baclofen and valproic acid on capsaicin-induced cough in normal volunteers

GABA analogues and GABA(B) agonists have antitussive effects in the cat and the guinea-pig. However, as its effect is unknown in the human, we studied the influence of 20 mg baclofen, the GABA(B) agonist and 800 mg valproic acid, a GABA-transaminase inhibitor on capsaicin-induced cough in normal volunteers. Thirteen volunteers inhaled either saline or capsaicin at doses 0,4-50 nmol from a nebuliser controlled by a dosimeter. The number of coughs occurring in the 30 seconds following each inhalation were counted and the results expressed as the total cough response. There was no significant difference in D-2 or D-5 after baclofen or valproic acid pretreatment. However, when compared to baseline (time 0 h), the total cough response after 2 h differed significantly (p less than or equal to 0.05) after placebo, baclofen and valproic acid pretreatment. No differences between the treatment groups were found when the placebo response was taken into account. We conclude that capsaicin dose-response curves with regard to induced cough in healthy volunteers are not affected by single doses of valproic acid or baclofen, two drugs acting on GABA transmission, when tested two hours after oral administration.