2-(4-氨基-3-氯-5-三氟甲基苯基)-2-(叔丁氨基)-乙醇盐酸盐对气道平滑肌的松弛作用

Effect of 2-(4-amino-3-chloro-5-trifluomethyl-phenyl)-2-tert- butylaminoethanol hydrochloride on airway smooth muscle

目的:研究2-(4-氨基-3-氯-5-三氟甲基苯基)-2-(叔丁氨基)-乙醇盐酸盐(SPFF)对豚鼠气道平滑肌的松弛作用。方法:以盐酸异丙肾上腺素为对照考察SPFF对离体豚鼠气管条的松弛作用,及对离休豚鼠左心房的正性变时作用,并使用离体气管条考察特异性β_2受体阻滞剂ICI 118551对SPFF的拮抗作用。以沙丁胺醇为对照考察SPFF对豚鼠药物引喘的保护作用。通过放射配基竞争结合实验,测定了SPFF对肺组织β受体的特异结合。以蛋白竞争结合法考察了SPFF对肺内cAMP含量的升高作用。结果:SPFF对离休豚鼠气管条的松弛作用与异丙肾上腺素相当,且这一作用可被ICI 118551竞争性拮抗,而SPFF对离体豚鼠左心房的正性变时效应为异丙肾上腺素的60％,SPFF对β_2受体的选择性是异丙肾上腺素的163倍。SPFF对药物引起豚鼠喘息的保护作用比沙丁胺醇强约7倍,对肺内β受体的结合能力分别是异丙肾上腺素的4倍和沙丁胺醇的约200倍,而对肺组织内cAMP的升高作用约相当于同剂量沙丁胺醇的3倍。结论:SPFF是一种强效、高选择性的β_2受体激动剂。

Objective:To study the pharmacological effects of 4-amino-3-chloro-5-trifluomethyl-phenyl [2-(SPFF)-2-tert-butylamoino-ethanol hydrochloride] ,a newly synthesized β2 agonist,on some isolated tissues of guinea pigs or rats. Methods: The relaxation effect of SPFF on isolated tracheal strip of guinea pigs,and its positive chronotropic effect on isolated left atria of guinea pigs were studied by comparison with isoprenaline hydrochloride. The antagonist effect of ICI 118551 on SPFF was also studied by using isolated tracheal strip of guinea pigs. The protection effect of SPFF on induced asthma in guinea pigs was studied by comparison with salbutamol. The binding property of SPFF to β receptor in isolated lung strip of guinea pigs was studied by competitive binding test to 3H-DHA The effect of SPFF on cAMP level in isolated lung tissue of rats was performed by protein competitive binding assay. Results:The relaxation effect of SPFF on isolated tracheal strip of guinea pigs was comparative to that of isoprenaline hydrochloride, and could be competitively antagonized by ICI 118551. The positive chronotropic effect of SPFF on isolated left atria of guinea pigs was 60 % of that of isopreneline hydrochloride. And the selectivity of SPFF on β2 adrenoeceptor was 163 times to that of isoprenaline hydrochloride. The protective effect of SPFF on induced asthma in guinea pigs was 7 times stronger than that of salbutamol and the binding property of SPFF to β adrenoreceptor in isolated lung tissue was respectively 4 times and 200 times of that of isoprenaline hydrochloride and salbutamol. The enhanced effect of SPFF on cAMP level in isolated lung tissue of rats was 3 times that of salbutamol.Conclusion: SPFF is a potent β2 adrenoreceptor agonist with high selectivity.