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.