CI-949 is an allergic mediator release inhibitor that inhibits the release of leukotriene C4/D4 (LTC4/LTD4), histamine, and thromboxane B2 (TXB2) with IC50 values of 0.5 μM, 11.4 μM, and 0.1 μM, respectively.

TXB2:0.1 μM, LTC4:0.5 μM, Histamine:, LTD4:0.5 μM

Complete inhibition of leukotriene and thromboxane synthesis/release is obtained with 10 and 1 μM of CI-949, respectively. CI-949 is an effective inhibitor of the release of all three mediators in response to this stimulus. The IC50s for inhibition of histamine, leukotriene, and thromboxane are 6.3, 2, and 0.1 μM for the FMLP challenge [1]. CI-949 effectively inhibits the release of histamine and the synthesis or release of immunoreactive sulfidopeptide leukotrienes C4-D4 and thromboxane B2 from antigen-challenged lung fragments of actively sensitized guinea-pigs. The IC50s are 26.7±2.8 μM for histamine, 2.7±2.4 μM for leukotriene, and 3.0±1.8 μM for thromboxane [2].

A dose of 50 mg/kg i.p. of CI-949 protects conscious, aerosol-allergen challenged guinea-pigs for at least 1 h and 100 mg/kg i.p. or per os protects for at least 2 h. The animals are protected from collapse for at least I h after 50 and 100 mg/kg, and 100 mg/kg afforded complete protection up to 2h. An oral dose of 100 mg/kg at 2 h, but not at 4 h before challenge also inhibits collapse. A dose of 100 mg/kg at 4 h and again at 2 h before the challenge is more effective than a single dose at 2 h [2].