Terasawa M, Imayoshi T, Goto K
Nihon Yakurigaku Zasshi. 1983 Jul;82(1):93-101.
The effect of traxanox on SRS-A release was examined in vivo and compared with that of disodium cromoglycate (DSCG). Intravenous antigen challenge produced an intense anaphylactic bronchoconstriction that showed a peak time of 5 min in egg albumin-sensitized guinea pigs pretreated with three agents, mepyramine (2.5 mg/kg, i.v.), indomethacin (1 mg/kg, i.v.) and propranolol (0.05 mg/kg, i.v.). This bronchoconstriction was almost completely inhibited by additional pretreatment with an SRS-A antagonist, FPL 55712 (2.5 mg/kg, i.v.). A lipoxygenase inhibitor, BW755C (10 mg/kg, i.v.), also significantly inhibited this reaction. These results indicate that this anaphylactic bronchoconstriction is due to the release of endogenous SRS-A. In this model, traxanox (5 and 10 mg/kg, i.v.) showed a dose-related inhibition, but DSCG (10 mg/kg, i.v.) did not. FPL 55712 (1 mg/kg, i.v.) administered at the peak time of the bronchoconstriction caused a relaxation. Traxanox, on the other hand, failed to relax this reaction. In IgE-mediated rat passive peritoneal anaphylaxis (PPA), traxanox (0.01--10 micrograms/rat, i.p.) inhibited the release of SRS-A and histamine dose-dependently. This inhibitory effect was about 10--20 times as potent as that of DSCG. In addition, both traxanox (0.1 microgram/rat, i.p.) and DSCG (1 microgram/rat, i.p.) showed a synergistic effect in combination with isoproterenol (0.01 microgram/rat, i.p.) and an additive effect with theophylline (100 micrograms/rat, i.p.) in inhibiting the release of SRS-A in rat PPA. These results suggest that traxanox inhibits the release of SRS-A in vivo, so that it may be clinically effective in treating patients with allergic bronchial asthma.
在体内研究了曲安西龙对慢反应物质-A（SRS-A）释放的影响，并与色甘酸二钠（DSCG）进行了比较。静脉内抗原激发在预先用三种药物（甲吡胺，2.5mg/kg，静脉注射；吲哚美辛，1mg/kg，静脉注射；普萘洛尔，0.05mg/kg，静脉注射）预处理的卵白蛋白致敏豚鼠中引起强烈的过敏性支气管收缩，其在5分钟时达到峰值。用SRS-A拮抗剂FPL 55712（2.5mg/kg，静脉注射）进行额外预处理几乎完全抑制了这种支气管收缩。脂氧合酶抑制剂BW755C（10mg/kg，静脉注射）也显著抑制了该反应。这些结果表明这种过敏性支气管收缩是由于内源性SRS-A的释放所致。在该模型中，曲安西龙（5和10mg/kg，静脉注射）呈现出剂量相关的抑制作用，但DSCG（10mg/kg，静脉注射）则没有。在支气管收缩的峰值时间给予FPL 55712（1mg/kg，静脉注射）可引起舒张。另一方面，曲安西龙未能使该反应舒张。在IgE介导的大鼠被动腹膜过敏反应（PPA）中，曲安西龙（0.01 - 10μg/只大鼠，腹腔注射）剂量依赖性地抑制SRS-A和组胺的释放。这种抑制作用比DSCG强约10 - 20倍。此外，在大鼠PPA中，曲安西龙（0.1μg/只大鼠，腹腔注射）和DSCG（1μg/只大鼠，腹腔注射）与异丙肾上腺素（0.01μg/只大鼠，腹腔注射）联合使用时均显示出协同作用，与茶碱（100μg/只大鼠，腹腔注射）联合使用时对抑制SRS-A释放具有相加作用。这些结果表明曲安西龙在体内抑制SRS-A的释放，因此它在临床上可能对治疗过敏性支气管哮喘患者有效。
