Acreozast

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.

1. The effect of TYB-2285, a novel anti-inflammatory drug, was investigated on passive peritoneal anaphylaxis in rats, and compared with disodium cromoglycate (DSCG), amlexanox, ketotifen fumarate and tranilast. 2. As parameters of passive peritoneal anaphylaxis, histamine release into the peritoneal cavity and capillary permeability elicited by ascitis were measured. 3. TYB-2285 (10 mg/kg), when given intraperitoneally at 0.5, 1 and 2 min before antigen challenge, inhibited anaphylactic histamine release by 36.2%, 57.5% and 52.6%, respectively. TYB-2285 also inhibited capillary permeability by 20.9%, 57.6% and 49.0%, respectively. 4. DSCG (10 mg/kg), given intraperitoneally 0.5 min before challenge, inhibited histamine release and capillary permeability by 79.6% and 57.6%, respectively. 5. Amlexanox (10 mg/kg), given intraperitoneally 0.5 min before challenge, inhibited histamine release and capillary permeability by 85.6% and 74.8%, respectively. 6. A time-course study showed that TYB-2285 (30 mg/kg) was effective for 30 min after oral administration. A dose-response study suggested that the inhibitory effect of TYB-22585 (postoperatively) on histamine release during PPA reached a plateau at 10 mg/kg. 7. In passive peritoneal anaphylaxis in vitro, TC-1121 and TC-1122, metabolites of TYB-2285, inhibited antigen-induced histamine release at 10(-7) to 10(-5) M in a dose-dependent manner, whereas TYB-2285 itself and other major metabolites of TYB-2285, TC-286 and TC-326, did not inhibit histamine release, even at 10(-4) M.