l Other popular name |
l (+/-)-2-(2-methoxyphen0xy)-menthyl-
3-ethoxycarbonylacetyl-1,3-thiazolidine;
l (R,S)-2-(2- methoxyphen0xy) -menthyl-
3-ethoxycarbonylacetyl-1,3-thiazolidine |
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l Discription and other details
l Cough is a common symptom of respiratory diseases associated with irritation or inflammation of the airways, and symptomatic antitussive drugs are frequently prescribed to control an abnormal cough reflex. Our aim was to evaluate the effects of moguisteine, a novel, peripheral, nonnarcotic antitussive agent, on airway inflammation induced in guinea-pigs with a variety of stimuli. These stimuli included exposure to tobacco smoke for 10 min, to elicit airway hyperreactivity, eosinophil recruitment in bronchoalveolar lavage (BAL), airway epithelial damage and plasma exudation; graded platelet-activating factor (PAF) infusion (600 ng.kg-1 over one h), to induce airway hyperreactivity; 2% ovalbumin (OA) aerosol challenge in 1% OA-sensitized animals, to induce late-phase (17 and 72 h) airway leucocyte accumulation. We also assessed the activity of moguisteine on plasma leakage induced by capsaicin, on bronchoconstriction induced by acetylcholine (ACh), histamine (H) and PAF, and on leukotriene mediated allergic bronchospasm in OA-sensitized guinea-pig. Moguisteine (p.o. and i.m.) and dexamethasone (p.o. and i.m.) dose-dependently reduced tobacco smoke-induced bronchial hyperreactivity. Moguisteine and dexamethasone abolished eosinophil recruitment in BAL, prevented the sloughing of the epithelium and significantly reduced airway microvascular leakage. Both agents were also highly effective in reducing bronchial hyperreactivity elicited by PAF infusion. In addition, moguisteine was active in inhibiting airway neutrophil and eosinophil accumulation in BAL observed 17 and 72 h after OA challenge in sensitized guinea-pigs. In contrast to dexamethasone, moguisteine did not prevent capsaicin-induced plasma leakage. It was also ineffective against bronchoconstriction as induced by ACh, H, and PAF and failed to inhibit leukotriene-dependent bronchospasm. Our data suggest that moguisteine represents an antitussive compound endowed with interesting airway anti-inflammatory properties in guinea-pigs in vivo. Its mechanism of action remains to be elucidated.
We have studied the effects of moguisteine, a new non-narcotic, peripherally acting antitussive compound, on tracheobronchial rapidly adapting irritant receptors (RARs). Experiments were carried out on dogs anaesthetized with a mixture of urethane and α-chloralose, paralysed with gallamine, vagotomized and artificially ventilated. Single unit action potentials identified as originating from tracheobronchial RARs were recorded from the peripheral cut end of the right vagus nerve. The activity of these receptors was recorded together with oesophageal pressure and arterial blood pressure. Fourteen RARs were challenged with moguisteine (200 μg.kg[-1] i.v.) in 0.4% dimethylsulphoxide (DMSO) or 0.4% DMSO alone (vehicle). Receptor activity was recorded before (control) and at 2, 5, 10, 15, 20, 30 and 45 min after administration of the challenging compounds. When the results at intervals of 2, 5, 10, 15 and 20 min were averaged for each dog, it was found that moguisteine decreased the mean activity of the 14 receptors to 75% of the control value (p<0.05); the greatest inhibition occurred 10-20 min after moguisteine administration. DMSO did not significantly affect the activity of these endings. Oesophageal pressure, arterial blood pressure and cardiac frequency were not altered during the experimental procedures. The overall results indicate the presence of an inhibitory effect of moguisteine on rapidly adapting irritant receptors that could account for the antitussigenic effect of this compound. (copided file) |
