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.