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Effect of azelastine on leukotriene synthesis in murine peritoneal cells and on thromboxane synthesis in human platelets.

Azelastine, a newly synthesized antiallergic agent, strikingly inhibited the production of leukotriene B4 and C4 (LTB4 and LTC4) in murine peritoneal cells which had been stimulated by calcium ionophore A23187. The 50% inhibitory concentrations (IC50) of the agent were approximately 1.0 x 10(-5) M. In addition, azelastine significantly inhibited also 5-lipoxygenase activity in peritoneal cells with an IC50 of 1.0 x 10(-5) M, but not on LTC4 synthetase, LTA4 hydrolase or phospholipase A2 activity. Furthermore, azelastine showed little effect on either 12-lipoxygenase activity or thromboxane synthesis in human platelets. These results suggest that at least the drug's antiallergic effects can be attributed to its inhibiting action of 5-lipoxygenase in regard to arachidonate metabolism.