EFFECTS OF MOGUISTEINE, A PERIPHERAL NONNARCOTIC ANTITUSSIVE AGENT, ON AIRWAY INFLAMMATION IN GUINEA-PIGS IN-VIVO

Cough is a common symptom of respiratory diseases associated with irri tation or inflammation of the airways, and symptomatic antitussive dru gs are frequently prescribed to control an abnormal cough reflex. Our aim was to evaluate the effects of moguisteine, a novel, peripheral, n onnarcotic antitussive agent, on airway inflammation induced in guinea -pigs with a variety of stimuli. These stimuli included exposure to to bacco smoke for 10 min, to elicit airway hyperreactivity, eosinophil r ecruitment in bronchoalveolar lavage (BAL), airway epithelial damage a nd plasma exudation; graded platelet-activating factor (PAF) infusion (600 ng . kg(-1) over one h), to induce airway hyperreactivity; 2% ova lbumin (OA) aerosol challenge in 1% OA-sensitized animals, to induce l ate-phase (17 and 72 h) airway leucocyte accumulation. We also assesse d the activity of moguisteine on plasma leakage induced by capsaicin, on bronchoconstriction induced by acetylcholine (ACh), histamine (H) a nd PAF, and on leukotriene mediated allergic bronchospasm in OA-sensit ized guinea-pig. Moguisteine (p.o. and i.m.) and dexamethasone (p.o. a nd im.) dose-dependently reduced tobacco smoke-induced bronchial hyper reactivity. Moguisteine and dexamethasone abolished eosinophil recruit ment in BAL, prevented the sloughing of the epithelium and significant ly reduced airway microvascular leakage. Both agents were also highly effective in reducing bronchial hyperreactivity elicited by PAF infusi on. In addition, moguisteine was active in inhibiting airway neutrophi l and eosinophil accumulation in BAL observed 17 and 72 h after OA cha llenge in sensitized guinea-pigs. In contrast to dexamethasone, moguis teine did not prevent capsaicin-induced plasma leakage. It was also in effective against bronchoconstriction as induced by ACh, H, and PAF an d failed to inhibit leukotriene-dependent bronchospasm. Our data sugge st that moguisteine represents an antitussive compound endowed with in teresting airway anti-inflammatory properties in guinea-pigs in vivo. Its mechanism of action remains to be elucidated. (C)ERS Journals Ltd 1996.