Inhibitory effect on the release of mediators from rat peritoneal exudate cells and antagonistic effect against mediators of MY-5116 and other anti-allergic agents

The effects of a new anti-allergic agent, MY-5116: isoamyl 5, 6-dihydro-7, 8-dimethyl-4, 5-dioxo-4H-pyrano [3, 2-c] quinoline-2-carboxylate, and its main metabolite, MY-1250: 5, 6-dihydro-7, 8-dimethyl-4, 5-dioxo-4H-pyrano [3, 2-c] quinoline-2-carboxylic acid, on 48 hr homologous PCA (PCA) in rats and the release of histamine and SRS from rat peritoneal exudate cells (PEC) induced by IgE antibody in comparison with other anti-allergic agents were investigated. Also, the effects of MY-5116 and MY-1250 on antagonistic action against histamine and LTD4 were studied. MY-5116, tranilast and ketotifen inhibited PCA at oral doses of more than 3 mg/kg, 300 mg/kg and 0.3 mg/kg, respectively. MY-1250, DSCG and tranilast inhibited significantly the release of histamine from PEC induced by the antigen-antibody reaction in a dose-dependent manner, and the values of IC50 were 4.9 × 10-8, 4.8 × 10-6 and 4.6 × 10-6 g/ml, respectively. Ketotifen inhibited significantly the release of histamine at a concentration of 10-5 g/ml, but it accelerated significantly the release of histamine from PEC at a concentration of 10-4 g/ml. MY-1250 and tranilast suppressed the release of SRS from PEC induced by the antigen-antibody reaction. The values of IC50 of MY-1250 and tranilast were 1.5 × 10-6 and 2.1 × 10-6g/ml, respectively. MY-1250 suppressed slightly the release of SRS from PEC induced by A23187. MY-5116 showed no effect on the increase of vascular permeability induced by histamine, bradykinin and serotonin in rats. MY-5116 and MY-1250 showed no antagonistic action on the bronchial contraction and the contraction of isolated ileum and trachea induced by LTD4 in guinea pigs. Theses results suggest that the MY-5116 and MY-1250 do not have antagonistic action against chemical mediators, and the anti-allergic action of MY-5116 is based on the inhibitory effect of MY-1250, the main active metabolite of MY-5116, on the release of chemical mediators.