Correlating the clinical actions and molecular mechanisms of general anesthetics
Correlating the clinical actions and molecular mechanisms of general anesthetics
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DOI：
10.1097/aco.0b013e32816678a5
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发表时间：
2007-08-01
影响因子：
2.5
通讯作者：
Forman, Stuart A.
中科院分区：
文献类型：
--
作者：
Solt, Ken;Forman, Stuart A.
综述目的综述近年来全身麻醉药作用的分子机制的体内外研究进展，包括临床表现不同的几类全身麻醉药通过不同的分子靶点诱导遗忘、催眠和不动。异丙酚、依托咪酯和巴比妥类药物通过增强特异性γ-氨基丁酸A型受体的活性，产生深度遗忘和催眠，但不动性较弱。相比之下，一氧化二氮、氙和氯胺酮通过抑制谷氨酸和烟碱受体并激活钾“泄漏”通道（如TREK-1）产生镇痛作用，但催眠作用和遗忘作用较弱。挥发性卤代麻醉剂对分子靶点几乎没有选择性。它们作用于上面提到的所有通道，以及其他靶点，如甘氨酸受体和神经递质释放的介质。SummarySeveral clinical distinct 'anesthesia states'是由不同类别的药物通过不同的分子靶点作用于神经元回路引起的。了解全身麻醉药的治疗和毒性作用的机制有助于我们将麻醉的“艺术”重新定义为一门“科学”。这些研究还加强了开发具有改善临床效用的新药的努力。
Purpose of reviewTo summarize recent in-vitro and in-vivo research on molecular mechanisms of general anesthetics' actions.Recent findingsClasses of general anesthetics with distinct clinical profiles appear to induce amnesia, hypnosis, and immobility via different molecular targets. Propofol, etomidate, and barbiturates produce profound amnesia and hypnosis, but weak immobility, by enhancing the activity of specific gamma-aminobutyric acid typeA receptors. In contrast, nitrous oxide, xenon, and ketamine produce analgesia, but weak hypnosis and amnesia, by inhibiting glutamate and nicotinic receptors and activating potassium 'leak' channels such as TREK-1. Volatile halogenated anesthetics show little selectivity for molecular targets. They act on all the channels mentioned above, and other targets such as glycine receptors and mediators of neurotransmitter release.SummarySeveral clinically distinct 'anesthetic states' are induced by different classes of drugs acting on neuronal circuits via different molecular targets. Understanding the mechanisms underlying the therapeutic and toxic actions of general anesthetics helps us reframe the 'art' of anesthesia into more of a 'science'. These studies also enhance efforts to develop new drugs with improved clinical utility.