Effects of specific tachykinin receptor antagonists on citric acid-induced cough and bronchoconstriction in unanesthetized guinea pigs

Abstract

We compared the effects of a tachykinin NK 1 receptor antagonist, FK888 ( N 2-[(4 R)-4-hydroxy-1-(1-methyl-1 H-indol-3-yl)carbonyl- l-prolyl]- N-methyl- N-phenylmethyl-3-(2-naphtyl)- l-alaninamide), and a tachykinin NK 2 receptor antagonist, SR48968 (( S)- N-methyl- N[4-(4-acetylamino-4-phenyl-piperidino)-2-(3,4-dichlorophenyl)butyl]benzamide]), on citric acid-induced cough and bronchoconstriction in conscious guinea pigs. FK888 and SR48968 inhibited the cough dose dependently. Combination of FK888 and SR48968 showed a small additive effect compared with that of FK888 or SR48968 alone. SR48968 but not FK888 inhibited the bronchoconstriction dose dependently. These results indicate that tachykinin NK 1 receptors as well as tachykinin NK 2 receptors are involved in the citric acid-induced cough response. The antitussive activity of the tachykinin NK 1 receptor antagonist appeared not to depend on the anti-bronchoconstrictor effects.