Studies on a new antiallergic pyridinecarboxamide TA-5707F and its sodium salt (TA-5707). II. Mechanism of antiallergic action of TA-5707.

Abstract

Abstract-Mechanism of the antiallergic action of 6-methyl-N-(1 H-tetrazol-5-yl) 2-pyridinecarboxamide (TA-5707F) was studied using the water-soluble sodium salt (TA-5707). 1) TA-5707 administered p.o. at the dose ca. 3 times the ID50 for the PCA reaction did not inhibit capillary dye leakage induced on the rat skin by intracutaneous injection of histamine, serotonin, bradykinin and leukotriene D4 (LTD4). 2) TA-5707, at concentrations above 10-7 M, inhibited antigen-induced histamine release and dye leakage in the rat peritoneal cavity (passive peritoneal anaphylaxis). 3) TA-5707 inhibited both anaphylactic and compound 48/80 induced histamine release from the rat peritoneal mast cells, the IC50 being ca. 10-5 M in both cases. It was concluded that TA-5707F exerts its antiallergic action by inhibiting the release of chemical mediators from sensitized cells.

N,N′-[(2,3,5,6-Tetrafluoro-1,4-phenylene)dimethylene]bis(pyridine-4-carboxamide)

“…Pyridinecarboxamide derivatives have attracted much attention because of their biological activity. Some derivatives of pyridinecarboxamide possess anticancer (Liu et al, 1996) and anti-allergic activities (Tsuzurahara et al, 1987), and are efficient as IKK inhibitors (Li & Prakash, 2005), monoamine oxidase B inhibitors (Blauenstein et al, 1998) and anticonvulsant drugs (Palmer et al, 1993). As part of a search for new pyridinecarboxamide compounds with better biological activity, the title compound, (I), has been synthesized.…”