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(acetoxyacety lamino)-4-chlorobenzonitrile), was investigated in ovalbumin-sensitize d 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 cyanosi s, but not the bronchoconstriction. TYB-2285, given singly or consecut ively, inhibited the appearance of late asthmatic response and the inf iltration of inflammatory cells, such as eosinophils, into the airway. Additionally, airway hyper-responsiveness was also reversed by the si ngle administration of TYB-2285. Luminol-dependent chemiluminescence o f 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 b y inhibiting the accumulation of eosinophils and other inflammatory ce lls into the airway, and also by inhibiting the production of oxygen r adicals from airway-infiltrated cells.