TY - JOUR T1 - Role of Voltage-Gated Sodium Channels in the Mechanism of Ether-Induced Unconsciousness JF - Pharmacological Reviews JO - Pharmacol Rev SP - 450 LP - 466 DO - 10.1124/pr.118.016592 VL - 71 IS - 4 AU - Nicholas Denomme AU - Jacob M. Hull AU - George A. Mashour A2 - Isom, Lori L. Y1 - 2019/10/01 UR - http://pharmrev.aspetjournals.org/content/71/4/450.abstract N2 - 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. ER -