Effect of KW-4679, an Orally Active Anti-allergic Drug, on Antigen-Induced Airway Hyperresponsiveness in Actively Sensitized Guinea Pigs

Abstract

ABSTRACT-We investigated the effect of propylidene]-6,11-dihydro dibenz [b,e]oxepin-2-acetic acid monohydrochloride), an orally active anti-allergic drug, on antigen-in duced airway hyperresponsiveness using two different indicators, pulmonary resistance (RL) and dynamic lung compliance (Cdyn), in actively sensitized guinea pigs. Oral administration of KW-4679 (0.1 and 1 mg/kg) 1 hr before aerosolized antigen exposure significantly inhibited the development of airway hyper responsiveness to inhaled acetylcholine in RL and Cdyn in a dose-dependent manner. Terfenadine (10 mg/kg) also inhibited the development of airway hyperresponsiveness. These results indicate that KW-4679 could be useful in the treatment of bronchial asthma.

Pharmacological, Pharmacokinetic and Clinical Properties of Olopatadine Hydrochloride, a New Antiallergic Drug

“…Kawasaki et al also investigated the effect of olopatadine on antigen-induced airway hyperresponsiveness to inhaled acetylcholine using R L and dynamic lung compliance (C dyn ) in actively sensitized guinea pigs under anesthesia. Oral administration of olopatadine (0.1 and 1 mg/ kg) significantly inhibited the development of airway hyperresponsiveness to inhaled acetylcholine in R L and C dyn (13). Examination of the bronchoalveolar lavage fluid 24 h after antigen challenge revealed the inhibitory effect of olopatadine (1, 3 and 10 mg/ kg, p.o.)…”

“…LAR is known to be accompanied by an increase in bronchial responsiveness to nonspecific stimulation and by the infiltration of inflammatory cells into the bronchial lumen. The effects of olopatadine on the development of bronchial hyperresponsiveness, airway inflammation and early and late asthmatic responses following aerosol antigen challenge in guinea pigs which were actively sensitized by the inhalation of aerosolized ovalbumin were investigated (12,13). As an index of bronchoconstriction in conscious guinea pigs, respiratory resistance (R L ), was automatically measured by a wholebody plethysmograph (14).…”