Inhibitory Effects of Non-narcotic Antitussive Drugs on Cholinergically and Non-cholinergically Mediated Neurogenic Contractions of Guinea-pig Isolated Bronchial Muscle

Abstract

We have examined the actions of non-narcotic antitussive drugs on the response evoked by electrical field stimulation or by acetylcholine (ACh) and neurokinin A (NKA) on guinea-pig bronchial strip chain. Electrical field stimulation (1-32 Hz, 0.5 ms, 30 V for 5 s) evoked a biphasic contraction in a frequency-dependent manner, consisting of a cholinergically mediated fast contraction followed by a non-cholinergically mediated slow contraction. Dextromethorphan (1-300 microM) and tipepidine (0.1-100 microM) caused a concentration-dependent inhibition in the height of the biphasic contraction, but noscapine (1-300 microM) was less effective. Submaximal contractions of bronchial muscle evoked by exogenous ACh (1-30 microM) were inhibited by tipepidine (10-100 microM), but not by dextromethorphan (10-100 microM) or noscapine (10-100 microM), while those evoked by exogenous NKA (10-300 nM) were augmented by these drugs. The results indicate that in guinea-pig isolated bronchial muscle, dextromethorphan inhibited both neurally-mediated responses but not those to the exogenously applied agent. Tipepidine caused an inhibition similar to the non-cholinergically mediated response of dextromethorphan, it also caused a more profound inhibition of the cholinergically mediated response and selectively antagonized ACh. Noscapine had no effect.