Mechanism of action of an anti-allergic compound; 2,4-bis(2-acetoxy-benzamido) benzoic acid (AB-50): inhibition of anaphylactic and non-anaphylactic histamine release from rat peritoneal mast cells.

Abstract

The mechanism of the inhibitory effect of the newly synthesized compounds, 2, 4-bis (2-acetoxybenzamido) benzoic acid (AB-50) and 2, 4-bis (2-hydroxybenzamido) benzoic acid (AB-23, an active form of AB-50) on IgE-like antibody-mediated passive cutaneous anaphylaxis (PCA) was studied in comparison with that of disodium cromoglycate (DSCG). AB-50 had no anti-inflammatory activity in carrageenin edema assay, nor did it inhibit dermal reactions elicited by local injection of histamine, serotonin, or bradykinin. AB-23 markedly inhibited rat mast cell degranulation (RMCD) in vitro following IgE-anti-IgE interaction and antigen-induced histamine release in the rat peritoneal cavity. It was concluded that the inhibition of IgE-mediated PCA by AB-50 was based on prevention of degranulation of and thus release of chemical mediators from mast cells without direct antagonism against chemical mediators of PCA. AB-23 also inhibited non-anaphylactic histamine release from rat peritoneal mast cells induced by Compound 48/80 or dextran. While all of these activities were also shared by DSCG, AB-23 was found to be more active than DSCG with respect to inhibition of RMCD and histamine release induced by Compound 48/80.