Abstract: Using ³H-WB 4101 binding assay in rat cerebral cortex membranes, effects of 18 mexiletine derivatives on alpha₁-adrenoceptors were studied in order to find new antihypertensive alpha₁ receptor blocking agents. The results showed that 6 of them showed significant affinities to alpha₁-adrenoceptors in rat cerebral cortex membranes. Some structureactivity relationship were found, among them only the compounds with chiral carbon showed high affinity to alpha₁-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 pA₂ 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 α₁ receptor antagonists.