ANTIALLERGIC ACTION OF BETOTASTINE BESILATE (TAU-284) IN ANIMAL-MODELS - A COMPARISON WITH KETOTIFEN

The effects of betotastine besilate (betotastine: TAU-284), a novel an tiallergic drug, on homologous passive cutaneous anaphylaxis (PCA), me diator-induced cutaneous reaction, antigen-induced asthmatic responses and platelet-activating factor (PAF)-induced airway eosinophilia in s everal animal models, were compared to ketotifen. Betotastine (0.1 mg/ kg, p.o.) and ketotifen (1 mg/kg, p.o.) inhibited both rat PCA and his tamine-induced cutaneous reaction, whereas they showed little effect o n serotonin-induced cutaneous reaction. Betotastine (0.3 mg/kg, p.o.) and ketotifen (1 mg/kg, p.o.) significantly inhibited antigen-induced bronchoconstriction in guinea pigs which had been passively sensitized with guinea pig IgE antibody. In actively sensitized guinea pigs, the immediate and late phase increase in airway resistance (R-rs) were ob served within 5 min and between 4 and 7 h after the aeroantigen challe nge. Betotastine (1 mg/kg, p.o.) inhibited both responses. Ketotifen ( I mg/kg, p.o.) inhibited the immediate phase response, but did not aff ect the late phase response. Exposure of guinea pigs to aerosolized PA F increased the number of eosinophils in bronchoalveolar lavage fluid 24 h after the stimulation. Betotastine (3-10 mg/kg, p.o.) dose-depend ently inhibited PAF-induced accumulation of eosinophils in the broncho alveolar cavity. In contrast, cetirizine (10 mg/kg, p.o.) showed a ten dency to inhibit eosinophil accumulation, and ketotifen (10 mg/kg, p.o .) and terfenadine (10 mg/kg, p.o.) did not have any affect. These res ults indicate that betotastine could be useful in the treatment of all ergic disease such as bronchial asthma.