Effect of TYB-2285 on peritoneal anaphylaxis in passively sensitized rats.
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.
Department of Pharmacology, Pharmaceuticals Research Center, Toyobo Co., Ltd., Shiga, Japan.
A
A
Watanabe
T
T
Tominaga
H
H
Shutoh
H
H
Hayashi
J
J
Tsuji
D000707:Anaphylaxis / Q000188:drug therapy*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006636:Histamine Release / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D008297:Male; D009570:Nitriles / Q000494:pharmacology*; D010537:Peritoneum; D051381:Rats; D017208:Rats, Wistar
D000894:Anti-Inflammatory Agents, Non-Steroidal; D009570:Nitriles; C081050:3,5-bis(acetoxyacetylamino)-4-chlorobenzonitrile