EFFECT OF SR-140333, A TACHYKININ NK-1 ANTAGONIST,ON ANTIGEN-INDUCED AIRWAY HYPERRESPONSIVENESS IN SENSITIZED RATS

In the present study, the effects of SR-140333,｛(S)-1-(2-3,4-dichlorophenyl)-1-(3-isopropoxyphenylacetyl)piperidin-3ylethyl)-4-phenyl-1-azoniabicyclooctane·chloride｝, a nonpeptide antagonist for tachykinin NK-1 receptor, on the antigen-induced airway response to methacholine (MCh) aerosol and airway inflammation in sensitized SD rats were investigated. The baseline respiratory frequencies, tachypnea response to methacholine(MCh), the-log PC₃₀ values of MCh and the leukocyte counts in bronchoalveolar lavage significantly increased after inhalation of 1% oval albumin(OA) aerosol. SR-140333 (152 nmol·kg^-1, ip) or dexamethasone(368 nmol·kg^-1, ip), bid×3　d inhibited these responses. SR-140333 at a low dose of 0.01 mg·kg^-1 showed an incomplete inhibition. From these results, we conclude that antigen challenge causes airway hyperresponsiveness and airway inflammation and that tachykinin NK-1 receptor antagonist inhibits these responses. 