Abstract
Compound FPL 55712 is a highly selective antagonist of SRS-A derived from guinea-pig, rat, man and dog. It equally antagonizes SRS (slow reacting substance) released by calcium ionophore from rat basophilic leukemia cells and peritoneal mono-nuclear cells and by compound 48/80 from cat paw. In comparatively high doses FPL 55712 significantly inhibits passive cutaneous anaphylaxis in rat and anaphylactic bronchoconstriction in guinea-pig and rat and antigen-induced rhythmic mechanical activity in chicken ileum and late phase of Schultz-Dale reaction in guinea-pig trachea and human bronchus. In addition, FPL 55712 inhibits the SRS-A-induced release of rabbit aorta contracting substance (RCS) from guinea-pig lung. FPL 55712 facilitates sputum clearance in allergic canine asthma. This compound also inhibits the guinea-pig ECF-A (eosinophil chemotactic factor of anaphylaxis)-induced eosinophil chemotactic response of guinea-pig eosinophils in vitro. Compound FPL 55712 is an invaluable pharmacological tool for the identification of SRS(A) and to help define the role of SRS-A in the pathophysiology of immediate hypersensitivity (e.g. anaphylaxis and allergic asthma). Clinical trials of FPL 55712 as an aerosol in allergic obstructive respiratory diseases in man and animals may help to further understand the mechanism(s) and chemical mediator(s) involved in these conditions.
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