Solt Ken, Forman Stuart A
Department of Anesthesia and Critical Care, Massachusetts General Hospital, Boston, MA 02114, USA.
Curr Opin Anaesthesiol. 2007 Aug;20(4):300-6. doi: 10.1097/ACO.0b013e32816678a5.
To summarize recent in-vitro and in-vivo research on molecular mechanisms of general anesthetics' actions.
Classes 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.
Several 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.
总结近期关于全身麻醉药作用分子机制的体外和体内研究。
具有不同临床特征的全身麻醉药类别似乎通过不同分子靶点诱导失忆、催眠和不动。丙泊酚、依托咪酯和巴比妥类药物通过增强特定的A型γ-氨基丁酸受体活性产生深度失忆和催眠，但致不动作用较弱。相比之下，氧化亚氮、氙气和氯胺酮通过抑制谷氨酸和烟碱受体并激活钾“渗漏”通道（如TREK-1）产生镇痛作用，但催眠和失忆作用较弱。挥发性卤代麻醉药对分子靶点的选择性较小。它们作用于上述所有通道以及其他靶点，如甘氨酸受体和神经递质释放介质。
不同类别的药物通过不同分子靶点作用于神经回路，诱导出几种临床上不同的“麻醉状态”。了解全身麻醉药治疗和毒性作用的潜在机制有助于我们将麻醉“艺术”更多地重塑为一门“科学”。这些研究也加强了开发具有更好临床效用的新药的努力。
