Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Madrid, Spain.
Chirality. 2012 Nov;24(11):944-50. doi: 10.1002/chir.22051. Epub 2012 Jun 7.
Local anesthetics are useful probes of ion channel function and structure. Stereoselective interactions are especially interesting because they can reveal three-dimensional relationships between drugs and channels with otherwise identical biophysical and physicochemical properties. Furthermore, stereoselectivity suggests direct and specific receptor-mediated action, and identification of such stereospecific interactions may have important clinical consequences. The fact that drug targets are able to discriminate between the enantiomers present in a racemic drug is the consequence of the ordered asymmetric macromolecular units that form living cells. However, almost 25% of the drugs used in the clinical practice are racemic mixtures, and their individual enantiomers frequently differ in both their pharmacodynamic and pharmacokinetic profiles. Moreover, their effects can be similar to or different from the pharmacological effect of the drug and may contribute to the undesired effects of the drug. In other cases, the pharmacological effects induced by the two enantiomers on the molecular target are opposite. In the present manuscript, we will review the stereoselective effects of bupivacaine-like local anesthetics on cardiac sodium and potassium channels.
局部麻醉剂是研究离子通道功能和结构的有用探针。立体选择性相互作用尤其有趣，因为它们可以揭示药物和通道之间的三维关系，而这些通道具有相同的生物物理和物理化学性质。此外，立体选择性表明了直接和特定的受体介导作用，并且鉴定这种立体特异性相互作用可能具有重要的临床意义。药物靶标能够区分外消旋药物中存在的对映异构体的事实是形成活细胞的有序不对称大分子单元的结果。然而，临床上使用的药物中几乎有 25%是外消旋混合物，它们的单个对映异构体在药效学和药代动力学特征上经常不同。此外，它们的作用可能与药物的药理作用相似或不同，并可能导致药物的不良作用。在其他情况下，两种对映异构体对分子靶标诱导的药理作用是相反的。在本手稿中，我们将回顾布比卡因类局部麻醉剂对心脏钠和钾通道的立体选择性作用。
