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Abstract-Sites of the inhibitory action of antiallergic drugs (azelastine, oxatomide, tranilast, repirinast and amlexanox) on human neutrophils were investigated by measuring leukotriene B4 formation, arachidonic acid release and superoxide generation. Results obtained in this study were as follows: (1) Formations of leukotriene B4 by neutrophils activated with a calcium ionophore (A23187) were effectively inhibited by all types of antiallergic drugs examined here, although the required concentrations were within a range of 20-200 /tM. (ii) Releases of arachidonic acid from activated cells were diminished by azelastine and oxatomide that were classified as basic antiallergic drugs. On the contrary, acidic antiallergic agents including repirinast, amlexanox and tranilast enhanced the arachidonic acid liberation. (iii) Generations of superoxide from neutrophils activated with either phorbol 12-myristate 13-acetate or n-formyl-methionyl-leucyl-phenylalanine were effectively diminished only by the basic antiallergic drugs.

Sites of the inhibitory actions of antiallergic and antihistaminic drugs on polymorphonuclear leukocytes were examined by means of measurements of arachidonic acid release, superoxide anion generation and changes in membrane potential. The results obtained in this study were as follows. (i) Azelastine, an antiallergic drug, inhibited arachidonic acid release as well as superoxide generation. However, high concentrations of azelastine diminished the charge of the cells. (ii) Clemastine, used as an antihistamine, was as effective as azelastine on the metabolic bursts of leukocytes, including changes of membrane potential in leukocytes. (iii) The selective inhibition of arachidonic acid release was achieved by ketotifen without appreciable effect on superoxide generation. The relationship among the changes of membrane potential, superoxide generation and arachidonic acid release is discussed.