Y. Kamikawa et Y. Shimo, SR-48968, A NOVEL NONPEPTIDE TACHYKININ NK-2-RECEPTOR ANTAGONIST, SELECTIVELY INHIBITS THE NONCHOLINERGICALLY MEDIATED NEUROGENIC CONTRACTION OF GUINEA-PIG ISOLATED BRONCHIAL MUSCLE, Journal of Pharmacy and Pharmacology, 45(12), 1993, pp. 1037-1041
We have examined the actions of SR 48968 ((S)-N-methyl-N-[4-(4-acetyla
mino-4-phenyl piperidino)-2-(3,4-dichlorophenyl) butyl] benzamide), a
novel non-peptide tachykinin NK-2-receptor antagonist, on the response
evoked by electrical field stimulation or by acetylcholine and neurok
inin A on guinea-pig isolated airway smooth muscle. Electrical field s
timulation (1-32 Hz, 0.3 ms, 30 V for 20 s) evoked a biphasic response
in a frequency-dependent manner, consisting of a cholinergically-medi
ated fast contraction followed by a non-adrenergically-mediated relaxa
tion in tracheal muscle and by a noncholinergically-mediated slow cont
raction in bronchial muscle. SR 48968 (0.01-1 mu M) caused a concentra
tion-dependent inhibition of non-cholinergically mediated contraction
of bronchial muscle, without significant influence on cholinergically
and non-adrenergically-mediated responses. Submaximal contractions of
tracheal and bronchial muscles evoked by exogenous neurokinin A (10-30
0 nM) were markedly inhibited by SR 48968 (0.1-1 mu M), but those by e
xogenous acetylcholine (1-3 mu M) were slightly inhibited by the antag
onist. The results indicate that in guinea-pig isolated bronchial musc
le, SR 48968 selectively inhibited non-cholinergically mediated neurog
enic contraction via antagonism of NK-2 receptors.