Effects of moguisteine, a peripheral nonnarcotic antitussive agent, on airway inflammation in guinea-pigs in vivo

Abstract

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.

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

“…The time course of its inhibitory effect on RAR activity, with a rapid onset and a relatively long-lasting action, should contribute to its therapeutic value. The findings of an inhibitory effect of moguisteine on inflammatory processes [4,5], particularly at the airway levels, support the involvement of RARs in the mechanism of action of this antitussive compound. In fact, some of the components of inflammation, such as pulmonary congestion, microvascular leakage, mucus secretion, hyperreactivity to cigarette smoke, acetylcholine and histamine, are known to stimulate RARs located in large extrapulmonary bronchi and, thus, to elicit cough [34].…”

“…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].…”

“…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].…”

Effect of Phosphodiestrase 4 Inhibitor (Rolipram)on Experimental Allergic Asthma-Guinea Pig Model

“…W badaniu parametrów biochemicznych i cytologicznych BALf stosowano 2 minutową inhalację 0,5% roztworem albuminy w PBS przy użyciu inhalatora dyszowego -MEDBRYT. Zwierzęta inhalowano roztworem antygenu, jednocześnie 5 świnek morskich w komorze o pojemności 17dcm 3 . W badaniu oporu oddechowego stosowano 2 minutową inhalację 0,5 % roztworem albuminy w PBS przy użyciu nebulizatora ultradźwiękowego Thomex L-2 z przepływem 1,2 ml/ min z wykorzystaniem prototypowego respiratora dla małych zwierząt (Instytut Biocybernetyki Polskiej Akademii Nauk).…”

“…Analiza płynu BAL. Ograniczenie przez glikokortykoidy napływu komórek do przestrzeni oskrzelowo-pęcherzykowej w przebiegu indukowanej OA reakcji astmatycznej u świnek morskich obserwowane w naszym doświadczeniu jest powszechnie znane i opisywane przez wielu badaczy (3,9,26) Przenikanie histaminy pochodzącej z degranulacji mastocytów śluzówki dróg oddechowych do przestrzeni oskrzelowo-pęcherzykowej w przebiegu reakcji astmatycznej jest faktem opisywanym w podręcznikach. Obserwowano to również w przedstawianej pracy, a dynamika wzrostu stężenia histaminy w BALf po prowokacji w naszych doświadczeniach jest zgodna z obserwacjami innych autorów (26).…”