美西律衍生物对α_1肾上腺素受体的作用

EFFECTS OF SOME MEXILETINE DERIVATIVES ON ALPHA1ADRENOCEPTORS

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Ｍ８５００１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（６８６）与ｐＫｉ（６５１）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 alpha1adrenoceptors were studied in order to find new antihypertensive alpha1 receptor blocking agents. The results showed that 6 of them showed significant affinities to alpha1adrenoceptors in rat cerebral cortex membranes. Some structureactivity relationship were found, among them only the compounds with chiral carbon showed high affinity to alpha1adrenoceptor. The affinity of compound M85001(pKi=651)was shown to be higher than that of tolazoline.In the rat anococcygeal muscle, compound M85001 competitively antagonized phenylephrineinduced contraction with pA2 value of 686 which is simillar to its pKi value in the binding assay.These findings may be of significance in the search for novel class of α1 receptor antagonists.