Action of moguisteine on the activity of tracheobronchial rapidly adapting receptors in the dog

Abstract

Moguisteine is an antitussive agent with a novel chemical structure [1]. Its pharmacological activity has been tested on experimental animals and in several clinical trials. In guinea-pigs, moguisteine was found to reduce cough elicited by citric acid inhalation and electrical stimulation of the airway mucosa as effectively as codeine and dextromethorphan [2]. Moguisteine, injected into the cerebral ventricles of guinea-pigs, does not inhibit electrically stimulated cough, which is, instead, effectively blocked by intraventricular codeine: these findings suggest that the antitussive action of moguisteine depends on a peripheral mechanism [3]. Naloxone, a known narcotic antagonist, reverses the antitussive effects of codeine, but not those of moguisteine, indicating that the effects of moguisteine do not involve any interaction with opiate receptors. The antitussive action of moguisteine is also accompanied by clear anti-inflammatory effects in conditions characterized by bronchial hyperreactivity, airway leucocyte recruitment and airway microvascular leakage [4,5]. These anti-inflammatory effects of moguisteine have been found to be as strong as those of dexamethasone [4,5]. Several clinical trials have substantiated the beneficial effects of moguisteine on coughs of various nature: upper airway infection, chronic bronchitis, pulmonary fibrosis and tumours [6][7][8][9][10][11].Since cough is a reflex response elicited through the activation of specialized receptors activated by exogenous irritants and/or spontaneously occurring pathological conditions, the antitussive action of moguisteine could be viewed as dependent on an inhibitory effect on rapidly adapting irritant receptors (RARs). Indeed, the aim of this study was to investigate the possible effect of moguisteine on the activity of tracheobronchial RARs.RARs, as first identified by KELLER and LOESER [12] and later characterized with single fibre recordings by KNOWLTON and LARRABEE [13], represent a group of airway stretch receptors that respond to maintained lung in-flation and deflation with a rapidly adapting discharge at a highly irregular pattern of discharge. The rate of adaptation varies considerably among RARs, with the most rapidly adapting endings responding only during changes in stretch with a behaviour similar to Pacinian corpuscles, showing a clear off-response at the removal of the stim-ulus [14]. RARs are very responsive to intraluminal stim-uli, mechanical probing of the mucosa, inhalation of inert dust, inflammatory mediators and oedema of the airway walls [15]; for this reason they have also been called irritant receptors [16]. The mechanosensitivity (response to inflation) of RARs is second only to that of slowly adapting receptors and higher than that of pulmonary and bronchial C-fibre endings [17].RARs of similar nature are located superficially within the mucosa of both larynx and tracheobronchial tree [18]. RARs located in the large extrapulmonary tracheobronchial airways (trachea, main stem bronchi and proximal When the results a...