Effect of TYB-2285 on early and late bronchial responses and airway hyperreactivity in actively sensitized guinea pigs.

1. The effect of a new antiasthmatic drug, TYB-2285 [3,5-bis (acetoxyacetylamino)-4-chlorobenzonitrile], on dual bronchoconstriction and airway hyperreactivity in actively sensitized guinea pigs was investigated. 2. Immediate and late bronchial responses were induced at 1-10 min and 4-7 hr after antigen inhalation, respectively. Guinea pigs were pretreated with TYB-2285 (300 mg kg(-1) PO, as a single dose or consecutively for 7 days). 3. The immediate bronchial response was inhibited only by a multiple administration of TYB-2285. Late bronchial response was inhibited by both administration methods. 4. The numbers of eosinophils, neutrophils and macrophages, but not lymphocytes, in the bronchoalveolar lavage fluid were increased at 4 hr after antigen inhalation. TYB-2285, given singly and consecutively, decreased the numbers of total cells, eosinophils, neutrophils and macrophages. 5. Sensitized guinea pigs showed significant airway hyperreactivity to inhaled histamine. This airway hyperresponsiveness was reversed by a single administration of TYB-2285. 6. Luminol-dependent chemiluminescence of airway-infiltrated cells was slightly inhibited by TYB-2285 (20 microg ml(-1)). 7. The present study shows that TYB-2285 inhibits late asthmatic response and airway hyperresponsiveness, presumably by inhibiting the accumulation and activation of eosinophils and other inflammatory cells.