[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- 3yl]ethyl)-4-phenyl-1-azoniabicyclo[2.2.2]octane.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, i.p.) or dexamethasone(368 nmol.kg-1, i.p.), bid x 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.
Zhang
W P
WP
Laboratory of Neurobiology, Zhejiang Medical University, Hangzhou 310031.
Zhao
M H
MH
Tian
J
J
Yu
Y P
YP
Chen
J S
JS
Wei
E Q
EQ
D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D007958:Leukocyte Count; D008297:Male; D016210:Methacholine Chloride; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000494:pharmacology*; D011812:Quinuclidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration / Q000187:drug effects; D012130:Respiratory Hypersensitivity / Q000139:chemically induced / Q000276:immunology* / Q000503:physiopathology
D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D011812:Quinuclidines; D016210:Methacholine Chloride; C085215:SR 140333; D003907:Dexamethasone