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 bro nchoconstriction induced by histamine and capsaicin and in man protect s 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 differen t receptors and fibers (i.e. metacholine via cholinergic receptors and ultrasonically nebulized distilled water (UNDW) via histamine and neu ropeptide release). The study design is randomized, double-blind, cros s-over versus placebo in 30 allergic asthmatic patients. Baseline bron chial tone and bronchoconstrictor response to metacholine (MCh) were n ot modified by active treatment nor by placebo. On the contrary, in ai rway 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 less-than-or -equal-to 0.05] in comparison to no effect for placebo. Similarly, in airway responsiveness to specific allergen, active treatment antagoniz ed 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% confi dence interval 0.07-1.04; p < 0.05), respectively. No antagonist effec t was evident with placebo at all times. Besides inhibiting cough, LD is also partially effective in inhibiting bronchial hyperreactive resp onse against specific allergen and UNDW bronchoconstriction. Hence, LD might act by partly inhibiting histamine and neuropeptide release.