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

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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 μM) and tipepidine (0.1–100 μM) caused a concentration-dependent inhibition in the height of the biphasic contraction, but noscapine (1–300 μM) was less effective. Submaximal contractions of bronchial muscle evoked by exogenous ACh (1–30 μM) were inhibited by tipepidine (10–100 μM), but not by dextromethorphan (10–100 μM) or noscapine (10–100 μM), 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.