四氢原小檗碱同类物对α_1肾上腺素受体的拮抗作用  

ANTAGONISTIC EFFECT OF TETKAHYDKOPROBERBEKINE HOMOLOGUES ON α1-ADRENOCEPTOR

作　　者：吕志珍[1] 魏璇 金国章[1] 韩启德 

机构地区：[1]北京医科大学第三医院血管医学研究所,中国科学院上海药物研究所

出　　处：《药学学报》1996年第9期652-656,共5页Acta Pharmaceutica Sinica

摘　　要：用放射配体结合实验与离体血管收缩功能实验相结合的方法，研究了４种四氢原小檗碱（ｔｅｔｒａｈｙｄｒｏｐｒｏｂｅｒｂｅｒｉｎｅ，ＴＨＰＢ）同类物对α＿１－肾上腺素受体（α＿１－ＡＲ）的作用。结果显示左旋四氢巴马汀（ｌ－ＴＨＰ），左旋千金藤立陡碱（ｌ－ＳＰＤ），四氢原小檗碱－１８（ＴＨＰＢ－１８）和四氢小檗碱（ＴＨＢ）￣（１２５)ＩＢＥ２２５４￣（１２５)Ｉ－２－β（４－ｈｙｄｒｏｘｙｐｈｅｎｙｌ）－ｅｔｈｙａｍｉｎｏｍｅｔｈｙｌ－ｔｅｔｒａｌｏｎｅ，￣（１２５)ＩＢＥ）与大鼠脑皮质α＿１－ＡＲ的结合呈竞争性拮抗作用，ｐＫ１值分别为５．５４±０．３６，５．５６±０．４７，５．７５±０．５６和６．０１±０．６０，Ｈｉｌｌ系数接近于１．０。并拮抗苯肾上腺素（ｐｈｅｎｙｌｅｐｈｒｉｎｅ，ＰＥ）介导大鼠主动脉的收缩，ｐＡ＿２值分别为５．４８±０．５８，５．６６±０．５４，５．６４±０．３４和５．４５±０．７６，斜率与１．０无显著性差别。结果提示，４种四氢原小檗碱同类物对α＿１－ＡＲ均有非亚型选择性拮抗效应，且亲和性相同。The antagonistic effect of tetrahydroproberberine(THP)homologues on α1-adrenoceptor was studied by combination of radioligand binding assays and measurements ofvasoconstriction responses.The results showed that l-tetrahydropalmatine(l-THP),l- stepholidine(l-SPD),THPB-18 and tetrahydroberberine(THB)competitively inhibited the 125 I-BE2254 specificbinding in rat cerebral cortex with pK1 values of 5.54±0.36,5.56±0.47,5.75±0.56 and 6.01 ±0.60,respectively,and the Hill efficiency was not significantly different from unity.They inhibitedphenylephrine-induced constrictions with pA2 values of 5.48 ± 0.58,5. 66 ± 0. 54,5.64 ± 0.34 and5.45 ± 0.76,respectively,and the slopes of Schild plot were not significantly different from unity。The results indicate that the 4 THP homologues are nonsubtype selective competitive antagonists forα1-adrenoceptor with similar affinities。

关 键 词：四氢原小檗碱 L-THP L-SPD 肾上腺受体 拮抗作用 

分 类 号：R978[医药卫生—药品]