PHARMACOLOGICAL PROPERTIES OF N‐(3′,4′‐DIMETHOXYCINNAMOYL) ANTHRANILIC ACID (N‐5′), A NEW ANTI‐ATOPIC AGENT

Abstract

N‐(3′,4′‐dimethoxycinnamoyl) anthranilic acid (N‐5′) exhibited a dose‐dependent, potent inhibition of the passive cutaneous anaphylaxis (PCA) mediated by homocytotropic antibodies (HTA), which was hardly affected by anti‐inflammatory agents such as phenylbutazone, indomethacin and prednisolone at any dose used. The HTA‐induced PCA was significantly inhibited by combined treatment with diphenhydramine and cyproheptadine. Doses of N‐5′ which potently inhibited HTA‐induced PCA inhibited only slightly the heterologous PCA produced by anti‐bovine serum albumin (BSA) rabbit serum. This heterologous PCA was clearly inhibited by phenylbutazone, indomethacin and prednisolone. Diphenhydramine and cyproheptadine, singly or combined inhibited the heterologous PCA only slightly. The increased vascular permeability caused by histamine and 5‐hydroxytryptamine was significantly inhibited by diphenhydramine or cyproheptadine, but not by N‐5′ and the anti‐inflammatory agents used. N‐5′ 150 mg/kg orally inhibited rat paw oedema induced by carrageenin by about 26% while phenylbutazone, indomethacin and prednisolone produced significant inhibition. N‐5′ at concentrations of 100 and 1000 μm significantly inhibited (by about 52% and 95%, respectively) the histamine release from rat peritoneal cells induced by HTA; 10 μm N‐5′ had little effect. Histamine release was inhibited by phenylbutazone or indomethacin at 1000 μm but not at 100 μm. Prednisolone had no effect on histamine release at any of the concentrations used. These findings suggest that the inhibition of the HTA‐induced PCA by N‐5′ may be due to inhibition of histamine release and is clearly different from the actions of anti‐inflammatory agents such as phenylbutazone, indomethacin and prednisolone. 1976 British Pharmacological Society