Levodropropizine (LD) activity in allergic asthmatic patients, challenged with ultrasonically nebulized distilled water, metacholine and allergen-induced bronchospasm.
The antitussive compound Levodropropizine (LD) is active in animal bronchoconstriction induced by histamine and capsaicin and in man protects from bronchoconstriction induced by capsaicin. The primary objective of this study was to evaluate the mechanism of action of LD given at 60 mg t.i.d. as oral drops, for 8 days by means of specific bronchial challenges (allergens) and of aspecific challenges acting via different receptors and fibers (i.e. metacholine via cholinergic receptors and ultrasonically nebulized distilled water (UNDW) via histamine and neuropeptide release). The study design is randomized, double-blind, cross-over versus placebo in 30 allergic asthmatic patients. Baseline bronchial tone and bronchoconstrictor response to metacholine (MCh) were not modified by active treatment nor by placebo. On the contrary, in airway responsiveness to UNDW, the active treatment showed an antagonist effect against induced bronchoconstriction of 59% [activity ratio (AR) as antilog = 0.41; 95% confidence interval 0.35-0.54; p < or = 0.05] in comparison to no effect for placebo. Similarly, in airway responsiveness to specific allergen, active treatment antagonized the bronchoconstrictor effect of grass pollen by 83% and of various allergens (dermatophagoides and grass pollen) by 72%, i.e. AR of 0.17 (95% confidence interval 0.045-0.65; p < 0.01) and of 0.28 (95% confidence interval 0.07-1.04; p < 0.05), respectively. No antagonist effect was evident with placebo at all times. Besides inhibiting cough, LD is also partially effective in inhibiting bronchial hyperreactive response against specific allergen and UNDW bronchoconstriction. Hence, LD might act by partly inhibiting histamine and neuropeptide release.
Bossi
R
R
Institute of Respiratory Diseases, University of Milan, Italy.
Banfi
P
P
Filipazzi
V
V
Castelli
C
C
Braga
P C
PC
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000485:Allergens; D000996:Antitussive Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001249:Asthma / Q000517:prevention & control*; D016535:Bronchial Hyperreactivity / Q000517:prevention & control; D001985:Bronchial Provocation Tests; D001986:Bronchial Spasm / Q000517:prevention & control*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000517:prevention & control*; D008297:Male; D016210:Methacholine Chloride; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D010919:Placebos; D011409:Propylene Glycols / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D014464:Ultrasonic Therapy; D014867:Water
D000485:Allergens; D000996:Antitussive Agents; D010919:Placebos; D011409:Propylene Glycols; D014867:Water; D016210:Methacholine Chloride; C035916:dipropizine