2I1430 Antitussive effect of NS-398, a selective COX-2 inhibitor, in guinea-pigs

Several reports have demonstrated that the capsaicin-induced coughs were increased in the presence of prostaglandins in the airway. Moreover, it has been reported that the expression of COX-2, that converts arachidonic acid to prostaglandins, was detectable in cultured human airway epithelial cells in the absence of inflammatory cytokine stimulation. Thus, it is possible that COX-2 inhibitor may produce an antitussive effect. To test this hypothesis, we investigated the effects of NS-398, a selective COX-2 inhibitor, and SC-560, a selective COX-1 inhibitor, on the capsaicin-induced coughs in guinea-pigs. NS-398 (1 - 10 mg/kg, p. o. ) dose-dependently and significantly reduced the number of capsaicin-induced coughs. However, SC-560 (10 mg/kg, p. o. ) did not reduce the number of capsaicin-induced coughs. The antitussive effect of NS-398 (10 mg/kg, p. o. ) was not antagonized by pretreatment with methysergide, a non-selective 5-HT receptor antagonist, (3mg/kg, i. p. ). The present study clearly demonstrated that COX-2 inhibitor, but not COX-1 inhibitor, exhibits a potent antitussive effect. Furthermore, it is possible that the antitussive action of NS-398 depends mainly on peripheral mechanisms since 5-HT receptors have an important role for the cough-depressant activities of centrally acting, but not peripheral acting, antitussive drugs. These results suggest that COX-2 inhibitors may have a therapeutical benefit in reducing the coughs.