PT  - JOURNAL ARTICLE
AU  - Nicholas Denomme
AU  - Jacob M. Hull
AU  - George A. Mashour
ED  - Isom, Lori L.
TI  - Role of Voltage-Gated Sodium Channels in the Mechanism of Ether-Induced Unconsciousness
AID  - 10.1124/pr.118.016592
DP  - 2019 Oct 01
TA  - Pharmacological Reviews
PG  - 450--466
VI  - 71
IP  - 4
4099  - http://pharmrev.aspetjournals.org/content/71/4/450.short
4100  - http://pharmrev.aspetjournals.org/content/71/4/450.full
SO  - Pharmacol Rev2019 Oct 01; 71
AB  - 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.