Inhibitory effect of olopatadine hydrochloride (KW-4679), a novel antiallergic drug, on peptide leukotriene release from human eosinophils

Abstract

Olopatadine hydrochloride (olopatadine; KW-4679), (Z)-11-[(3-dimethylamino)propylidene]-6,11-dihydro-dibenz[b,e]oxepin-2-acetic acid monohydrochloride, is an antiallergic drug with selective and potent histamine H 1 receptor antagonist activity. In the present study, we investigated the effect of olopatadine on the release of peptide leukotrienes (P-LT), potent inflammatory mediators, from human eosinophils. Human eosinophils were purified from venous blood of healthy donors by negative selection using the anti-CD16 antibody. When human eosinophils were stimulated with the calcium ionophore A23187 (1 μmol/L), the amount of P-LT release was approximately 1200 pg/ 10 5 cells, while thromboxane (TX) B 2 release was under the detection limit (< 20 pg/10 5 cells). Olopatadine inhibited the A23187-induced P-LT release from human eosinophils with an IC50 of 4.5 μmol/L. Ketotifen also inhibited this reaction with an IC 50 of 39.4 μmol/L. The inhibitory effect of olopatadine on the P-LT release may contribute to the antiallergic efficacy of this drug.