Abstract: Tetrandrine possesses calcium antagonistic and hypotensive effects. It was cleaved into two compounds O-methylcoclaurine (Ⅰ) and N-methylarmepavine (Ⅱ) by Na/NH₃. Pharmacological test indicated that Ⅰ and Ⅱ showed weaker calcium antagonistic activity but having α-adrenoceptor antagonistic effect.With Ⅰ and Ⅱ as lead compounds as well as integration of some structural feature of calcium antagonists and SAR of antiarrhythmic drugs, two kindsof substituted tetrahydroisoquinoline derivatives Ⅲ, Ⅳ were designed and synthesized in order to search for novel cardiovascular drugs.Tetrahydroisoquinoline compounds were first synthesized by the Bischler-Napiraski cyclization with substituted phenethylamine and aromatic acetic acid or substituted cinnamic acid as starting materials. N-alkylsubstituted tetrahydroisoquinoline compounds were prepared by the reaction of 4 with alkyl halide to produce 5, then reduction of 5 by KBH₄ to give Ⅲ_13～25. The synthesis of N-alkylaminoethyl substituted tetrahyroisoquinoline compounds involved the reaction of 6 with chloroacetyl chloride to obtain Ⅳ_1～3, the reaction of Ⅳ_1～3 with secondary amineto produce 9, and then reduction of 9 with LiAlH₄ to give Ⅳ_16-19.Preliminary tests showed that most of these compounds exhibited varied degree of α-adrenoceptor antagonistic effect, and some of them possess calcium antagonistic activity. In anesthetic normal rats Ⅲ_15,19 showed certain degree of hypotensive effect. Ⅳ_10,11 exhibited significant protective effect on experimental arrhythmic animals. The results of quantum chemical calculation of some compounds demonstrate that the compounds might act with α₁-adrenoceptor by forming charge-transfer complex.