Emerging molecular mechanisms of general anesthetic action.
General anesthetics are essential to modern medicine, and yet a detailed understanding of their mechanisms of action is lacking. General anesthetics were once believed to be "drugs without receptors" but this view has been largely abandoned. During the past decade significant progress in our understanding of the mechanisms of general anesthetic action at the molecular, cellular and neural systems levels has been made. Different molecular targets in various regions of the nervous system are involved in the multiple components of anesthetic action, and these targets can vary between specific anesthetics. Neurotransmitter-gated ion channels, particularly receptors for GABA and glutamate, are modulated by most anesthetics, at both synaptic and extrasynaptic sites, and additional ion channels and receptors are also being recognized as important targets for general anesthetics. In this article, these developments, which have important implications for the development of more-selective anesthetics, are reviewed in the context of recent advances in ion channel structure and function.
Hemmings
Hugh C
HC
Departments of Anesthesiology and Pharmacology, Weill Cornell Medical College, 1300 York Avenue, Box 50, New York, NY 10021, USA. hchemmi@med.cornell.edu
Akabas
Myles H
MH
Goldstein
Peter A
PA
Trudell
James R
JR
Orser
Beverley A
BA
Harrison
Neil L
NL
D000768:Anesthesia, General; D000777:Anesthetics / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D006801:Humans; D007473:Ion Channels / Q000378:metabolism*; D008024:Ligands; D018079:Receptors, GABA / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism
D000777:Anesthetics; D007473:Ion Channels; D008024:Ligands; D018079:Receptors, GABA; D016194:Receptors, N-Methyl-D-Aspartate