Inhibitory effects of oxatomide on several activities of SRS-A and synthetic leukotrienes in guinea-pigs and rats.

Abstract

Effects of oxatomide, an orally active anti-allergic drug, on several activities of slow reacting substance of anaphylaxis (SRS-A) and synthetic leukotrienes (LT) C4, D4 and E4 were investigated. In addition, such activities of oxatomide were compared with those of FPL-55712. Oxatomide, at a concentration of 3 X 10(-8) M or higher, inhibited the phasic contractions of isolated guinea-pig ileum induced by partially purified SRS-Agp and SRS-Arat which were anaphylactically generated from guinea-pig lung fragments and rat peritoneal cavities, respectively. The 50% inhibitory concentrations (IC 50) of oxatomide to the contractions by SRS-Agp and SRS-Arat are 2.7 +/- 0.9 X 10(-7) M and 1.6 +/- 0.3 X 10(-7) M, respectively. Oxatomide also inhibited the LTC4, LTD4, histamine or serotonin-induced contractions of ileum. FPL-55712, a specific SRS-A antagonist, inhibited SRS-Agp, SRS-Arat, LTC4 or LTD4-induced contractions at concentrations ranging from 10(-9) M to 10(-6) M without affecting histamine and serotonin responses. Oxatomide produced dose-dependent relaxations of isolated guinea-pig tracheal and lung parenchymal strips precontracted with LTD4 and histamine. Oxatomide, at doses 10 and 30 mg/kg (p.o.), inhibited significantly the increase in vascular permeability produced by LTC4, LTE4, histamine and serotonin in rats. These results suggest that, although less effective and less selective as compared with FPL-55712, oxatomide exerts inhibitory effects on SRS-A activities, and that such effects could partly explain the anti-allergic effects of the compound.