Departments of Pharmacology (N.D.) and Anesthesiology (G.A.M.), Center for Consciousness Science (N.D., G.A.M.), and Neuroscience Graduate Program (J.M.H., G.A.M.), University of Michigan, Ann Arbor, Michigan.
Departments of Pharmacology (N.D.) and Anesthesiology (G.A.M.), Center for Consciousness Science (N.D., G.A.M.), and Neuroscience Graduate Program (J.M.H., G.A.M.), University of Michigan, Ann Arbor, Michigan
Pharmacol Rev. 2019 Oct;71(4):450-466. doi: 10.1124/pr.118.016592.
Despite continuous clinical use for more than 170 years, the mechanism of general anesthetics has not been completely characterized. In this review, we focus on the role of voltage-gated sodium channels in the sedative-hypnotic actions of halogenated ethers, describing the history of anesthetic mechanisms research, the basic neurobiology and pharmacology of voltage-gated sodium channels, and the evidence for a mechanistic interaction between halogenated ethers and sodium channels in the induction of unconsciousness. We conclude with a more integrative perspective of how voltage-gated sodium channels might provide a critical link between molecular actions of the halogenated ethers and the more distributed network-level effects associated with the anesthetized state across species.
尽管全身麻醉药已经临床应用了 170 多年，但它们的作用机制仍未完全阐明。在这篇综述中，我们重点介绍了电压门控钠离子通道在卤代醚类镇静催眠作用中的作用，描述了麻醉机制研究的历史、电压门控钠离子通道的基本神经生物学和药理学，以及卤代醚类诱导意识丧失与钠离子通道之间的机制相互作用的证据。最后，我们从更综合的角度来看待电压门控钠离子通道如何为卤代醚类的分子作用与麻醉状态下跨物种相关的更分布式网络级效应之间提供关键联系。
