Effectiveness of levodropropizine against cigarette smoke-induced airway hyperreactivity: possible mechanism.
We verified the possible effect of the new antitussive drug levodropropizine on airway hyperreactivity and lung inflammation induced by cigarette smoke exposure in anaesthetized guinea-pigs. Levodropropizine, administered by aerosol at 25 mg/ml for 30 s completely prevented smoke induced airway hyperreactivity. The protective effect was early in onset (3 min) and lasted up to 30 min. The same dose of codeine, administered in the form of an aerosol, decreased the increase in airway responsiveness induced by smoke inhalation slightly but not significantly. In parallel with the functional results, levodropropizine also inhibited the recruitment of inflammatory cells triggered by smoke exposure within the airway lumen. When levodropropizine was administered i.v. to anaesthetized guinea-pigs, it reduced the bronchocontractile effect of capsaicin dose-dependently, whereas it was without effect against substance P-induced bronchoconstriction. These data demonstrate the ability of levodropropizine to counteract the hyperreactive phenomenon and the associated inflammatory event induced by cigarette smoke exposure, an effect which might depend on its capacity to modulate the activation of the peptidergic system.
Daffonchio
L
L
Institute of Pharmacological Sciences, University of Milan, Italy.
Hernandez
A
A
Melillo
G
G
Clavenna
G
G
Omini
C
C
D000403:Airway Resistance / Q000187:drug effects*; D000818:Animals; D000996:Antitussive Agents / Q000494:pharmacology*; D016084:Bronchoconstriction / Q000187:drug effects*; D002211:Capsaicin / Q000037:antagonists & inhibitors / Q000633:toxicity; D003061:Codeine / Q000494:pharmacology; D006168:Guinea Pigs; D008297:Male; D011409:Propylene Glycols / Q000494:pharmacology*; D013373:Substance P / Q000037:antagonists & inhibitors / Q000633:toxicity; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
D000996:Antitussive Agents; D011409:Propylene Glycols; D014028:Tobacco Smoke Pollution; D013373:Substance P; D002211:Capsaicin; C035916:dipropizine; D003061:Codeine