Effect of SR-140333, a neurokinin-1 receptor antagonist, on airway reactivity to methacholine in sedated rats.
AIM
To study the roles of neurokinins in the airway reactivity (AR) to methacholine chloride (MC).


METHODS
The effects of (S)-1-(2-[3, 4-dichlorophenyl)-1-(3-isopropoxyphenylacetyl) piperidin-3-yl]ethyl)-4-phenyl-1-azoniabicyclo [2.2.2]octane.chloride (SR-140333), a neurokinin-1 receptor antagonist, on AR to inhaled MC in diazepam-sedated rats, and on MC-induced contraction of isolated tracheal spiral strips were observed.


RESULTS
SR-140333 inhibited the increase in respiratory rate (RR) induced by MC aerosol (10-1000 mumol/m3), and the ID50 for inhibiting the response to MC aerosol (1 mmol/m3) was 4.9 micrograms.kg-1 (95% confidence limits 1.4-17.2 micrograms.kg-1). SR-140333 1 mumol.L-1 had no inhibitory effect on MC-induced tracheal contraction. Atropine blocked responses to MC both in vivo and in vitro.


CONCLUSION
Endogenous neurokinins are involved in the AR to MC in rats, at least partly mediated via neurokinin-1 receptors.