INHIBITION OF LEUKOTRIENE SYNTHESIS BY TERFENADINE IN-VITRO

To determine the inhibitory mechanisms of terfenadine on the synthesis of leukotriene C-4 (LTC4), an important mediator in allergic diseases , we evaluated the action of terfenadine on the IgE-dependent producti on of LTC4 in rat basophilic leukaemia 2H3 cells. Rat IgE-loaded cells were stimulated with anti-lgE in the presence or absence of various c oncentrations of terfenadine and the level of LTC4 released into the m edium was measured by performing a specific radio immunoassay. Terfena dine inhibited the synthesis of LTC4 to 67.2% at a concentration of 5 mu g/ml. LT synthesis was directly suppressed by inhibition of 5-lipox ygenase (5-LO) through calcium ion-independent mechanisms, and was als o possibly suppressed by inhibition of cytosolic phospholipase A(2) an d 5-LO by blocking the influx of intracellular calcium ion that was in itiated by IgE-related stimulation.