The Effect of TYB-2285 on Dual Phase Bronchoconstriction and Airway Hypersensitivity in Guinea-pigs Actively Sensitized with Ovalbumin

The effect of a new anti-asthmatic drug, TYB-2285 (3,5-bis(acetoxyacetylamino)-4-chlorobenzonitrile), was investigated in ovalbumin-sensitized guinea-pigs. When guinea-pigs were pretreated with TYB-2285 (300 mg kg-1, p.o., single dose or consecutively for 7 days), the immediate asthmatic response was inhibited as demonstrated by diminished cyanosis, but not the bronchoconstriction. TYB-2285, given singly or consecutively, inhibited the appearance of late asthmatic response and the infiltration of inflammatory cells, such as eosinophils, into the airway. Additionally, airway hyper-responsiveness was also reversed by the single administration of TYB-2285. Luminol-dependent chemiluminescence of airway-infiltrated cells stimulated with A23187 was inhibited by TYB-2285 in a dose-dependent manner. The present study suggests that TYB-2285 inhibits late asthmatic response and airway hyperresponsiveness by inhibiting the accumulation of eosinophils and other inflammatory cells into the airway, and also by inhibiting the production of oxygen radicals from airway-infiltrated cells.