Emerging molecular mechanisms of general anesthetic action

被引:411
作者
Hemmings, HC
Akabas, MH
Goldstein, PA
Trudell, JR
Orser, BA
Harrison, NL
机构
[1] Weill Corner Med Coll, Dept Anesthesiol, New York, NY 10021 USA
[2] Weill Corner Med Coll, Dept Pharmacol, New York, NY 10021 USA
[3] Yeshiva Univ Albert Einstein Coll Med, Dept Physiol, Bronx, NY 10461 USA
[4] Yeshiva Univ Albert Einstein Coll Med, Dept Biophys, Bronx, NY 10461 USA
[5] Yeshiva Univ Albert Einstein Coll Med, Dept Neurosci, Bronx, NY 10461 USA
[6] Weill Corner Med Coll, Dept Anesthesiol, New York, NY 10021 USA
[7] Stanford Univ, Dept Anesthesia, Stanford, CA 94305 USA
[8] Univ Toronto, Dept Anesthesiol, Toronto, ON M5S 1A8, Canada
[9] Univ Toronto, Dept Physiol, Toronto, ON M5S 1A8, Canada
关键词
D O I
10.1016/j.tips.2005.08.006
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
引用
收藏
页码:503 / 510
页数:8
相关论文
共 71 条
  • [21] SYNTHESIS, BIOLOGICAL EVALUATION, AND PRELIMINARY STRUCTURE-ACTIVITY CONSIDERATIONS OF A SERIES OF ALKYLPHENOLS AS INTRAVENOUS ANESTHETIC AGENTS
    JAMES, R
    GLEN, JB
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 1980, 23 (12) : 1350 - 1357
  • [22] Evidence for a common binding cavity for three general anesthetics within the GABAA receptor
    Jenkins, A
    Greenblatt, EP
    Faulkner, HJ
    Bertaccini, E
    Light, A
    Lin, A
    Andreasen, A
    Viner, A
    Trudell, JR
    Harrison, NL
    [J]. JOURNAL OF NEUROSCIENCE, 2001, 21 (06)
  • [23] Nitrous oxide (laughing gas) is an NMDA antagonist, neuroprotectant and neurotoxin
    Jevtovic-Todorovic, V
    Todorovic, SM
    Mennerick, S
    Powell, S
    Dikranian, K
    Benshoff, N
    Zorumski, CF
    Olney, JW
    [J]. NATURE MEDICINE, 1998, 4 (04) : 460 - 463
  • [24] A designed four-α-helix bundle that binds the volatile general anesthetic halothane with high affinity
    Johansson, JS
    Scharf, D
    Davies, LA
    Reddy, KS
    Eckenhoff, RG
    [J]. BIOPHYSICAL JOURNAL, 2000, 78 (02) : 982 - 993
  • [25] EFFECTS OF VOLATILE ANESTHETICS ON THE KINETICS OF INHIBITORY POSTSYNAPTIC CURRENTS IN CULTURED RAT HIPPOCAMPAL-NEURONS
    JONES, MV
    HARRISON, NL
    [J]. JOURNAL OF NEUROPHYSIOLOGY, 1993, 70 (04) : 1339 - 1349
  • [26] General anesthetic actions in vivo strongly attenuated by a point mutation in the GABAA receptor β3 subunit
    Jurd, R
    Arras, M
    Lambert, S
    Drexler, B
    Siegwart, R
    Crestani, F
    Zaugg, M
    Vogt, KE
    Ledermann, B
    Antkowiak, B
    Rudolph, U
    [J]. FASEB JOURNAL, 2002, 16 (14) : 250 - +
  • [27] Agonist gating and isoflurane potentiation in the human γ-aminobutyric acid type A receptor determined by the volume of a second transmembrane domain residue
    Koltchine, VV
    Finn, SE
    Jenkins, A
    Nikolaeva, N
    Lin, A
    Harrison, NL
    [J]. MOLECULAR PHARMACOLOGY, 1999, 56 (05) : 1087 - 1093
  • [28] General anaesthetic actions on ligand-gated ion channels
    Krasowski, MD
    Harrison, NL
    [J]. CELLULAR AND MOLECULAR LIFE SCIENCES, 1999, 55 (10) : 1278 - 1303
  • [29] Methionine 286 in transmembrane domain 3 of the GABAA receptor β subunit controls a binding cavity for propofol and other alkylphenol general anesthetics
    Krasowski, MD
    Nishikawa, K
    Nikolaeva, N
    Lin, A
    Harrison, NL
    [J]. NEUROPHARMACOLOGY, 2001, 41 (08) : 952 - 964
  • [30] Krasowski MD, 2001, J PHARMACOL EXP THER, V297, P338