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 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.
Gallico
L
L
Boehringer Mannheim Italia, Research Center, Monza, Italy.
Oggioni
N
N
Dalla Rosa
C
C
Ceserani
R
R
Tognella
S
S
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000996:Antitussive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D016535:Bronchial Hyperreactivity / Q000188:drug therapy* / Q000473:pathology; D002211:Capsaicin / Q000494:pharmacology; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D007249:Inflammation / Q000188:drug therapy; D008297:Male; D012044:Regression Analysis; D012137:Respiratory System / Q000187:drug effects*; D012906:Smoke / Q000009:adverse effects; D013844:Thiazoles / Q000008:administration & dosage / Q000494:pharmacology*; D053778:Thiazolidines
D000893:Anti-Inflammatory Agents; D000996:Antitussive Agents; D012906:Smoke; D013844:Thiazoles; D053778:Thiazolidines; C087933:moguisteine; D003907:Dexamethasone; D000109:Acetylcholine; D002211:Capsaicin