Mitra Sukanya, Chopra Puneet
Departments of Anaesthesia and Intensive Care, Government Medical College and Hospital, Chandigarh, India.
Indian J Anaesth. 2011 Nov;55(6):556-62. doi: 10.4103/0019-5049.90608.
Many molecules can exist as right-handed and left-handed forms that are non-superimposable mirror images of each other. They are known as enantiomers or substances of opposite shape. Such compounds are also said to be chiral (Greek chiros meaning 'hand'). Such chiral molecules are of great relevance to anaesthetic theory and practice. This review summarizes the basic concepts, pharmacokinetic and pharmacodynamic aspects of chirality, and some specific examples of their application in anaesthesia, along with recent advances to elucidate the anaesthetic mechanisms. Chirality is relevant to anaesthesia, simply because more than half of the synthetic agents used in anaesthesia practice are chiral drugs. Almost all these synthetic chiral drugs are administered as racemic mixture, rather than as single pure enantiomers. These mixtures are not drug formulations containing two or more therapeutic substances, but combination of isomeric substances, with the therapeutic activity residing mainly in one of the enantiomer. The other enantiomer can have undesirable properties, have different therapeutic activities or be pharmacologically inert. Specific examples of application of chirality in anaesthetic drugs include inhalational general anaesthetics (e.g. isoflurane), intravenous anaesthetics (e.g. etomidate, thiopentone), neuromuscular blocking agents (e.g. cisatracurium), local anaesthetics (e.g. ropivacaine and levobupivacaine) and other agents (e.g. levosimendan, dexmedetomidine, L-cysteine). In the recent advances, chirality study has not only helped new drug development as mentioned above, but has also contributed in a more profound way to the understanding of the mechanism of anaesthesia and anaesthetic drugs.
许多分子可以以右手型和左手型的形式存在，它们是彼此不可重叠的镜像。它们被称为对映体或形状相反的物质。这类化合物也被称为手性化合物（希腊语“chiros”意为“手”）。这类手性分子与麻醉理论和实践密切相关。本文综述了手性的基本概念、药代动力学和药效学方面，以及它们在麻醉中的一些具体应用实例，以及阐明麻醉机制的最新进展。手性与麻醉相关，仅仅是因为麻醉实践中使用的合成药物一半以上是手性药物。几乎所有这些合成手性药物都是以外消旋混合物的形式给药，而不是单一的纯对映体。这些混合物不是含有两种或更多治疗物质的药物制剂，而是异构体物质的组合，其治疗活性主要存在于一种对映体中。另一种对映体可能具有不良性质、不同的治疗活性或无药理活性。手性在麻醉药物中的具体应用实例包括吸入性全身麻醉药（如异氟烷）、静脉麻醉药（如依托咪酯、硫喷妥钠）、神经肌肉阻滞剂（如顺式阿曲库铵）、局部麻醉药（如罗哌卡因和左旋布比卡因）以及其他药物（如左西孟旦、右美托咪定、L-半胱氨酸）。在最新进展中，手性研究不仅如上所述有助于新药开发，而且在更深刻的层面上有助于理解麻醉和麻醉药物的机制。
