新型抗过敏吡啶甲酰胺TA - 5707F及其钠盐（TA - 5707）的研究。II. TA - 5707抗过敏作用机制

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

作者信息

Tsuzurahara K, Ishikawa S, Ono Y, Murata T, Kikuchi M, Takeyama S

机构信息

Biological Research Laboratory, Tanabe Seiyaku Co., Ltd., Saitama, Japan.

出版信息

Jpn J Pharmacol. 1987 Sep;45(1):55-62. doi: 10.1254/jjp.45.55.

DOI:10.1254/jjp.45.55

PMID:2446038

Abstract

Mechanism of the antiallergic action of 6-methyl-N-(1H-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.

摘要

使用水溶性钠盐（TA-5707）研究了6-甲基-N-（1H-四唑-5-基）-2-吡啶甲酰胺（TA-5707F）的抗过敏作用机制。1）以约PCA反应ID50的3倍剂量口服给予TA-5707，并不抑制皮内注射组胺、5-羟色胺、缓激肽和白三烯D4（LTD4）诱导的大鼠皮肤毛细血管染料渗漏。2）浓度高于10（-7）M的TA-5707抑制抗原诱导的大鼠腹腔内组胺释放和染料渗漏（被动腹腔过敏反应）。3）TA-5707抑制大鼠腹腔肥大细胞中过敏反应性和化合物48/80诱导的组胺释放，两种情况下IC50均约为10（-5）M。得出结论，TA-5707F通过抑制致敏细胞释放化学介质发挥其抗过敏作用。