Inhibition of passive anaphylaxis induced in the rat hind paw and peritoneal cavity by N-(2-oxo-3,5,7-cycloheptatrien-1-yl)-aminooxoacetic acid ethyl ester (AY-25,674)

Abstract

Passive anaphylaxis induced in the rat hind paw and peritoneal cavity with rat serum containing immunoglobulin E antibody was inhibited by N-(2-oxo-3,5,7-cycloheptatrien-1-yl)-aminooxoacetic acid ethyl ester (AY-25,674). In contrast with disodium cromoglycate (DSCG), AY-25,674 was orally active. Otherwise, the activity profile of AY-25,674 was similar to that of DSCG. Peak activity occurred a short time after administration, large doses produced tachyphylaxis, and anaphylactic histamine release from mast cells was inhibited. AY-25,674 did not inhibit increased vascular permeability produced by nonreaginic antibody, compound 48/80, serotonin, or histamine. It is concluded that AY-25,674 produces its antiallergic effects by inhibiting mediator release from mast cells by a mechanism similar to that of DSCG.