Affinity and Selectivity of &bgr;‐Adrenoceptor Antagonists In Vitro
Affinity and Selectivity of &bgr;‐Adrenoceptor Antagonists In Vitro
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β-肾上腺素受体拮抗剂的体外亲和力和选择性
DOI：
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发表时间：
1985
影响因子：
3
通讯作者：
Belz Gg
中科院分区：
文献类型：
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作者：
A. Wellstein;D. Palm;Belz Gg
&NA;竞争放射性标记位点的儿茶酚胺（-）异丙肾上腺素（Iso）、（-）-去甲肾上腺素（NA）和（-）-肾上腺素（Adr）的效价顺序用于其药理学分类。结果表明，放射性配体3 H-CGP 12177仅标记大鼠唾液腺膜中的1-肾上腺素受体（Iso > NA > Adr）和大鼠网织红细胞中的2-肾上腺素受体（Iso > Adr ≥ NA）。然后使用这些模型推导经典肾上腺素受体拮抗剂（±）-普萘洛尔（prop; 2倍2选择性）和（±）-阿替洛尔（aten; 35倍1选择性）以及较新拮抗剂（±）倍他洛尔和（±）-比索洛尔（betax和biso;分别为35倍和75倍1选择性）的亚型选择性。具有最高选择性的配体是ICI 118，551（ICI），具有300倍的2亚型选择性。为了与给定血浆浓度下人体中的拮抗作用进行比较，在存在天然人血浆的情况下测量配体的平衡解离常数，并获得相对选择性标记亚型的平均值（Ki值，nmol/l）：prop：20，aten：250，biso：24，betax：23和ICI：2.5。
&NA; The potency order of the catecholamines (‐)isoprenaline (Iso), ( ‐ )‐noradrenaline (NA), and ( ‐ )‐adrenaline (Adr) in competition for radiolabelled sites is used for their pharmacological classification. It is shown that the radioligand 3H‐CGP 12177 exclusively labels &bgr;1‐adrenoceptors in rat salivary gland membranes (Iso > NA > Adr), and &bgr;2‐adrenoceptors in rat reticulocytes (Iso > Adr ≥ NA). These models are then used to derive the subtype‐selectivity of the classical &bgr;‐adrenoceptor antagonists (±)‐propranolol (prop; twofold &bgr;2‐selective) and (±)‐atenolol (aten; 35‐fold &bgr;1‐selective), as well as of the newer antagonists (±)betaxolol and (±)‐bisoprolol (betax and biso; 35‐fold and 75‐fold &bgr;1‐selective, respectively). The ligand with the highest selectivity is ICI 118,551 (ICI), with a 300‐fold &bgr;2‐subtype selectivity. For comparison with antagonistic effects in humans at given plasma concentrations, the equilibrium dissociation constants of the ligands are measured in the presence of native human plasma and yield values for the relative selectively labelled subtype in the mean (Ki‐values in nmol/l): prop: 20, aten: 250, biso: 24, betax: 23, and ICI: 2.5.