EFFECT OF TYB-2285 ON PERITONEAL ANAPHYLAXIS IN PASSIVELY SENSITIZED RATS

1. The effect of TYB-2285, a novel anti-inflammatory drug, was investi gated on passive peritoneal anaphylaxis in rats, and compared with dis odium cromoglycate (DSCG), amlexanox, ketotifen fumarate and tranilast , 2. As parameters of passive peritoneal anaphylaxis, histamine releas e into the peritoneal cavity and capillary permeability elicited by as citis were measured. 3. TYB-2285 (10 mg/kg), when given intraperitonea lly at 0.5, 1 and 2 min before antigen challenge, inhibited anaphylact ic histamine release by 36.2%, 57.5% and 52.6%, respectively. TYB-2285 also inhibited capillary permeability by 20.9%, 51.6% and 49.0%, resp ectively. 4. DSCG (10 mg/kg), given intraperitoneally 0.5 min before c hallenge, inhibited histamine release and capillary permeability by 79 .6% and 57.6%, respectively. 5. Amlexanox (10 mg/kg), given intraperit oneally 0.5 min before challenge, inhibited histamine release and capi llary 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 o ral administration. A dose-response study suggested that the inhibitor y effect of TYB-22585 (postoperatively) on histamine release during PP A reached a plateau at 10 mg/kg. 7. In passive peritoneal anaphylaxis in vitro, TC-1121 and TC-1122, metabolites of TYB-2285, inhibited anti gen-induced histamine release at 10(-7) to 10(-5) M in a dose-dependen t manner, whereas TYB-2285 itself and other major metabolites of TYB-2 285, TC-286 and TC-326, did not inhibit histamine release, even at 10( -4) M. (C) 1998 Elsevier Science Inc.