EFFECTS OF DS-4574, A NEW ORALLY ACTIVE ANTIALLERGIC AGENT, IN EXPERIMENTAL ALLERGIC AND INFLAMMATORY MODELS

The anti-allergic and anti-inflammatory activities of DS-4574, which p ossesses leukotriene antagonism and inhibits the release of immunologi cally stimulated mediators such as histamine and leukotrienes, were ev aluated in several animal models. DS-4574 had dose-dependent inhibitor y effects on IgE-mediated passive cutaneous anaphylaxis and the passiv e Arthus reaction in rats and the phase I response of Forssman antibod y-induced bronchoconstriction. In contrast, this compound had no effec t on the phase II response of Forssman antibody-induced bronchoconstri ction in guinea pigs, the reverse cutaneous anaphylaxis in rats, compl ement-dependent hemolysis of sheep erythrocytes and the delayed-type h ypersensitivity induced by methylated bovine serum albumin in mice. Th e results obtained in a double sensitization with two IgE antibodies s uggested that DS-4574, as well as disodium cromoglycate, did not impai r antigen-antibody combination but prevents the release of chemical me diators such as histamine. DS-4574 also had a weak inhibitory activity on carrageenin paw edema in rats, arachidonic acid ear edema in mice and adjuvant arthritis in rats. In addition, this compound inhibited i ncreased vascular permeability in rat skin induced by leukotriene D4 a nd platelet activating factor-induced pleurisy in rats in a dose-depen dent manner. These results indicate that DS-4574 inhibited type III al lergic reactions in addition to type I allergic reactions and some inf lammatory reactions. Therefore, DS-4574 could be useful in the treatme nt of allergic diseases such as asthma.