摘要
为寻找新的α1受体阻断剂,用[3H]WB4101配体测定法测定了18种美西律衍生物。结果表明,其中6种化合物对大鼠脑皮层α1受体有不同程度的亲和力。凡具有手性碳结构的化合物亲和力都较高。化合物M85001的亲和力较妥拉唑林(tolazoline)高一个数量级并能抑制苯肾上腺素引起的大鼠肛尾肌收缩,其pA2(686)与pKi(651)相近。结果提示,美西律衍生物对α1受体的亲和力可能与手性碳结构有关,从美西律衍生物中研制新的α1受体阻断剂是有前途的。
Using WB 4101 binding assay in rat cerebral cortex membranes, effects of 18 mexiletine derivatives on alpha1adrenoceptors were studied in order to find new antihypertensive alpha1 receptor blocking agents. The results showed that 6 of them showed significant affinities to alpha1adrenoceptors in rat cerebral cortex membranes. Some structureactivity relationship were found, among them only the compounds with chiral carbon showed high affinity to alpha1adrenoceptor. The affinity of compound M85001(pKi=651)was shown to be higher than that of tolazoline.In the rat anococcygeal muscle, compound M85001 competitively antagonized phenylephrineinduced contraction with pA2 value of 686 which is simillar to its pKi value in the binding assay.These findings may be of significance in the search for novel class of α1 receptor antagonists.
出处
《药学学报》
CAS
CSCD
北大核心
1998年第2期102-105,共4页
Acta Pharmaceutica Sinica
关键词
α1-受体阻断剂
美西律
放射配体结合法
Alpha1adrenoceptor blocking agent
Mexiletine derivatives
Radioligand binding assay