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Influences of the new compound MY-5116: isoamyl 5,6-dihydro-7,8-dimethyl-4,5-dioxo-4H-pyrano (3,2-C) quinoline-2-carboxylate and its metabolites were investigated on 48-hr rat homologous PCA (PCA) and the release of histamine from rat peritoneal mast cells induced by antigen antibody reaction (histamine release). MY-5116 (30 mg/kg) inhibited PCA significantly from 10 min to 2 hr after oral administration, and its ID50 (30 min) was 19.1 mg/kg. The inhibitory effect of its main metabolite, MY-1250, was the most potent among all the metabolites, 7HPQ, 8HPQ, 7CPQ and 8CPQ on the PCA (i.v.). Effect of MY-5116 suspended in 1% CMC on the PCA increased gradually after intravenous administration, but MY-1250 suppressed PCA immediately after intravenous injection. MY-5116 dissolved in DMSO in the concentration of 10(-7)-10(-6) g/ml didn't inhibit the histamine release, but the metabolite MY-1250 inhibited the histamine release. On the other experiment, MY-1250 inhibited the histamine release (IC50: 1.4 X 10(-7) g/ml), and MY-1250 was 17 times more potent than DSCG (2.4 X 10(-6) g/ml). From these results, it is suggested that MY-1250 is the main active metabolite of MY-5116.

Effects of MY-5116 on PCA reaction and on the histamine release from peritoneal cells induced by antigen antibody reactions.