olopatadine-hydrochloride and Bronchial-Hyperreactivity

We investigated the effects of KW-4679, an antiallergic drug, on the development of bronchial hyperresponsiveness, airway inflammation and early and late asthmatic responses following aerosol antigen challenge in guinea pigs actively sensitized by the inhalation of aerosolized ovalbumin. Pretreatment with KW-4679 (10 mg/kg, p.o.) 1 h before antigen challenge prevented the development of bronchial hyperresponsiveness to inhaled methacholine. Examination of the bronchoalveolar lavage fluid 24 h after antigen challenge revealed the inhibitory effect of KW-4679 on the infiltration of eosinophils into the airway. Treatment with KW-4679 significantly inhibited both the immediate and late asthmatic responses. These results indicate that KW-4679 could be useful in the treatment of allergic diseases such as bronchial asthma.

Topics: Administration, Oral; Airway Resistance; Animals; Anti-Allergic Agents; Antibody Formation; Antigens; Asthma; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; Cell Movement; Dibenzoxepins; Guinea Pigs; Male; Olopatadine Hydrochloride; Ovalbumin

We investigated the effect of KW-4679 ((Z)-11-[(3-dimethylamino)propylidene]-6,11-dihydrodibenz[b, e]oxepin-2- acetic acid monohydrochloride), an orally active anti-allergic drug, on antigen-induced 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 hyperresponsiveness 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.

Topics: Acetylcholine; Airway Resistance; Animals; Anti-Allergic Agents; Bronchial Hyperreactivity; Dibenzoxepins; Guinea Pigs; Lung Compliance; Male; Olopatadine Hydrochloride

We assessed the effects of KW-4679 on bronchoconstriction, airway hyperresponsiveness and infiltration of inflammatory cells into the bronchoalveolar lavage (BAL) fluid induced by platelet-activating factor (PAF) in guinea pigs. (1) KW-4679 (1, 10 mg/kg, p.o.) significantly inhibited PAF-induced bronchoconstriction in anesthetized, ventilated guinea pigs. Ketotifen (1, 10 mg/kg, p.o.) also significantly inhibited that reaction. (2) Intravenous administration of PAF (600 ng/kg/hr) to ventilated anesthetized guinea pigs induced bronchial hyperresponsiveness to histamine or substance P. PAF-induced bronchial hyperresponsiveness was significantly attenuated by pretreatment with KW-4679 (3 mg/kg, i.v.). (3) Exposure of guinea pigs to an aerosol of PAF induced an increase in the numbers of total leukocytes, eosinophils, neutrophils and lymphocytes in BAL fluid at 24 hr. KW-4679 (10 mg/kg, p.o.) reduced the increase in eosinophils in BAL fluid. Ketotifen (10 mg/kg, p.o.) partially reduced the increase in eosinophils in BAL fluid. (4) KW-4679 did not inhibit PAF-induced rabbit platelet aggregation. These observations indicate that KW-4679 attenuates the PAF-induced pulmonary reactions in guinea pigs and that these actions may be beneficial for the treatment of allergic bronchial asthma.

Topics: Animals; Anti-Allergic Agents; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; Bronchoconstriction; Dibenzoxepins; Guinea Pigs; Ketotifen; Leukocyte Count; Male; Olopatadine Hydrochloride; Platelet Activating Factor; Rabbits