Department of Anesthesiology, Asahi University School of Dentistry, Gifu, Japan.
Eur J Anaesthesiol. 2010 Sep;27(9):829-34. doi: 10.1097/EJA.0b013e32833bf5e4.
beta-Adrenoceptor-blocking agents have been used for perioperative management during anaesthesia, in which selective beta1-blockers are advantageous over nonselective beta-blockers. Apart from the different affinity for beta-adrenoceptors, beta1-blockers were differentially characterized in light of their different interaction with lipid membranes.
Selective (atenolol, metoprolol and esmolol) and nonselective (alprenolol, oxprenolol and propranolol) beta1-blockers were reacted at 0.2-1 mmol l with 1,2-dipalmitoylphosphatidylcholine liposomes and biomimetic membranes consisting of phospholipids, sphingolipid and cholesterol. Their membrane interactivities were comparatively determined using the potency to modify membrane fluidity by measuring fluorescence polarization. Their relative hydrophobicities were evaluated by reversed-phase liquid chromatography.
The chromatographic evaluation divided the tested drugs into more hydrophobic ones containing nonselective beta-blockers and less hydrophobic ones containing selective beta1-blockers. Nonselective beta-blockers, but not selective beta1-blockers, fluidized liposomal membranes, with the potency being oxprenolol < alprenolol < propranolol. Membrane-active alprenolol preferentially acted on the hydrophobic deeper regions of phospholipid bilayers. The potency of nonselective beta-blockers to fluidize biomimetic membranes was greatest in propranolol, followed by alprenolol and oxprenolol, whereas all selective beta1-blockers were inactive.
The membrane-fluidizing effects of beta-blockers are correlated with their relative hydrophobicities and their respective conformations to perturb the alignment of phospholipid acyl chains. The membrane-interacting characteristics differentiate beta-blockers as nonselective propranolol, alprenolol and oxprenolol vs. beta1-selective atenolol, metoprolol and esmolol. Such differentiation reflects not only the structural difference but also the beta-adrenoceptor-blocking difference. The membrane fluidization may be partly responsible for the nonselective blockade of beta-adrenoceptors.
β-肾上腺素受体阻滞剂已被用于麻醉期间的围手术期管理，其中选择性β1-受体阻滞剂优于非选择性β-受体阻滞剂。除了对β-肾上腺素受体的亲和力不同外，β1-受体阻滞剂在与脂质膜的不同相互作用方面也具有不同的特征。
选择性（阿替洛尔、美托洛尔和艾司洛尔）和非选择性（阿普洛尔、氧烯洛尔和普萘洛尔）β1-受体阻滞剂分别与 1,2-二棕榈酰基磷脂酰胆碱脂质体和由磷脂、鞘脂和胆固醇组成的仿生膜在 0.2-1mmol/L 下反应。通过测量荧光偏振来比较测定它们改变膜流动性的能力，从而比较它们的膜相互作用。通过反相液相色谱法评估它们的相对疏水性。
色谱评估将测试药物分为更疏水性的包含非选择性β-受体阻滞剂和更疏水性的包含选择性β1-受体阻滞剂。非选择性β-受体阻滞剂而非选择性β1-受体阻滞剂使脂质体膜流动化，其效力为氧烯洛尔<阿普洛尔<普萘洛尔。膜活性阿普洛尔优先作用于磷脂双分子层的疏水区。非选择性β-受体阻滞剂使仿生膜流动化的效力在普萘洛尔中最大，其次是阿普洛尔和氧烯洛尔，而所有选择性β1-受体阻滞剂均无活性。
β-受体阻滞剂的膜流动化效应与其相对疏水性及其各自的构象有关，这些构象会扰乱磷脂酰基链的排列。膜相互作用特性将β-受体阻滞剂区分非选择性普萘洛尔、阿普洛尔和氧烯洛尔与β1-选择性阿替洛尔、美托洛尔和艾司洛尔。这种差异不仅反映了结构差异，还反映了β-肾上腺素受体阻断差异。膜的流动化可能部分解释了非选择性β-肾上腺素受体阻断。
