@article {Denomme450, author = {Nicholas Denomme and Jacob M. Hull and George A. Mashour}, editor = {Isom, Lori L.}, title = {Role of Voltage-Gated Sodium Channels in the Mechanism of Ether-Induced Unconsciousness}, volume = {71}, number = {4}, pages = {450--466}, year = {2019}, doi = {10.1124/pr.118.016592}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {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{\textendash}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.}, issn = {0031-6997}, URL = {https://pharmrev.aspetjournals.org/content/71/4/450}, eprint = {https://pharmrev.aspetjournals.org/content/71/4/450.full.pdf}, journal = {Pharmacological Reviews} }