新型β2受体激动剂2-(4-氨基3-氯-5-三氟甲基苯基)-2-叔丁氨基-乙醇盐酸盐对映异构体抗哮喘作用的比较

Comparisons of antiasthmatic activities of racemic 2-(4-amino-3-chloro-5-trifluoromethylphenyl)-2-tertbutylaminoethanol hydrochloride,a novel adrenoceptor agonist,and its enantiomers

目的用整体动物实验法,比较2-(4-氨基-3-氯-5-三氟甲基苯基)-2-叔丁氨基-乙醇盐酸盐(2-(4-amino-3-chloro-5-trifluoromethylphenyl)-2-tert-butylaminoethanol hydrochloride,SPFF)对映异构体抗哮喘作用的效果和作用强度。方法用豚鼠肺溢流方法观察SPFF及其对映异构体的扩张气道平滑肌作用和强度;用小鼠气管酚红排泌实验和家鸽气管纤毛运动实验考察SPFF异构体的祛痰作用。结果十二指肠给药后60 min时,(-)-SPFF(30、10、3μg.kg-1)、(±)-SPFF(100、30、10μg.kg-1)、(+)-SPFF(100、30、10μg.kg-1)对组胺诱导的豚鼠支气管收缩都具有不同程度的抑制作用,(-)-SPFF的作用强度分别是(±)-SPFF和(+)-SPFF的1.4倍和5.7倍;(±)-SPFF(10、7.5、5 mg.kg-1)及其异构体对小鼠气道黏液分泌没有影响;(-)-SPFF(0.04、0.1 mg.kg-1)、(±)-SPFF(0.1、0.25 mg.kg-1)可显著促进气管纤毛运动,而(+)-SPFF对纤毛运动没有明显的促进作用;口服或静脉给予(-)-SPFF对小鼠的急性毒性低于(+)-SPFF。结论(-)-SPFF的抗哮喘作用优于(+)-SPFF。

Objective To compare the in vivo antiasthmatic activities of racemic 2-（4-amino-3-chloro-5-trifluoromethylphenyl）-2-tert-butylaminoethanol hydrochloride （SPFF） and its enantiomers. Methods Inhibitive effects on bronchoconstriction, induced by histamine in anesthetized guinea pigs using the Konzett and Ressler method, were investigated after the test drugs were given intraduodenally. Their effects on eliminating phlegm were tested in mice with the method of airway phenol red secretion as well as in pigeon with ciliary movement measurements. Results In the Konzett and Ressler experiment, （-）-SPFF was 1.4 and 5.7 times more potent than （±）-SPFF and （＋）-SPFF, respectively. （±）SPFF and both optical isomers exhibited no effects on airway mucilage secretion in mice;however, （-）-SPFF and （±）-SPFF could significantly accelerated ciliary movement in pigeon. Furthermore, the acute toxicity of （-）-SPFF was less potent than that of （＋）-SPFF. Conclusions The results indicate （-）-SPFF to be a powerful and safe single enantiomer of bronchodilator;it is superior than （＋）-SPFF in the treatment of asthma.