Modulation of NMDA receptor function by ketamine and magnesium. Part II: interactions with volatile anesthetics

Anesthesia and Analgesia
M W HollmannM E Durieux

Abstract

Mg2+ and ketamine interact superadditively at N- methyl-D-aspartate (NMDA) receptors, which may explain the clinical efficacy of the combination. Because patients are usually exposed concomitantly to volatile anesthetics, we tested the hypothesis that volatile anesthetics interact with ketamine and/or Mg2+ at recombinantly expressed NMDA receptors. NR1/NR2A or NR1/NR2B receptors were expressed in Xenopus oocytes. We determined the effects of isoflurane, sevoflurane, and desflurane on NMDA receptor signaling, alone and in combination with S(+)-ketamine (4.1 microM on NR1/NR2A, 3.0 microM on NR2/NR2B) and/or Mg2+ (416 microM on NR1/NR2A, 629 microM on NR1/NR2B). Volatile anesthetics inhibited NR1/NR2A and NR1/NR2B glutamate receptor function in a reversible, concentration-dependent, voltage-insensitive and noncompetitive manner (half-maximal inhibitory concentration at NR1/NR2A receptors: 1.30 +/- 0.02 minimum alveolar anesthetic concentration [MAC] for isoflurane, 1.18 +/- 0.03 MAC for desflurane, 1.24 +/- 0.06 MAC for sevoflurane; at NR1/NR2B receptors: 1.33 +/- 0.12 MAC for isoflurane, 1.22 +/- 0.08 MAC for desflurane, and 1.28 +/- 0.08 MAC for sevoflurane). On both NR1/NR2A and NR1/NR2B receptors, 50% inhibitory concentration...Continue Reading

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Citations

Oct 3, 2002·Journal of Neurosurgical Anesthesiology·Gina MateiIra S Kass
Feb 24, 2004·The Journal of Pharmacology and Experimental Therapeutics·Munehiro Shiraishi, R Adron Harris
Jul 28, 2004·Anesthesiology·Michael T Alkire, Lukasz A Gorski
Dec 6, 2006·American Journal of Veterinary Research·Patricia Queiroz-CastroTom Doherty
May 24, 2008·Anesthesia and Analgesia·Aubrey YaoJoseph F Antognini
Jun 8, 2012·BMC Anesthesiology·Robert J Brosnan, Roberto Thiesen
Apr 12, 2013·CNS Neuroscience & Therapeutics·Georges Mion, Thierry Villevieille
Jun 27, 2019·Journal of Neurophysiology·Fahad IqbalNaweed I Syed
Apr 23, 2020·Saudi Journal of Anaesthesia·Faris Al GhamdiJoseph D Tobias
Jul 2, 2020·Molecular Pharmacology·Jamie A Abbott, Gabriela K Popescu
Apr 22, 2008·Nature Reviews. Neuroscience·Nicholas P Franks
Jun 6, 2009·European Journal of Anaesthesiology·Andrea Kopp LugliChristoph H Kindler
Dec 2, 2015·Frontiers in Neural Circuits·Roxana A Stefanescu, Susan E Shore
Mar 8, 2017·Proceedings of the National Academy of Sciences of the United States of America·Karl F HeroldHugh C Hemmings
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Nov 18, 2015·A & a Case Reports·Baiba Senbruna, Jerrold Lerman
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Mar 16, 2019·Minerva anestesiologica·Maja Pavcnik, Mojca Groselj Grenc
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Apr 20, 2006·The Journal of Pharmacology and Experimental Therapeutics·Junichi OgataR Adron Harris
Sep 16, 2011·Anesthesia and Analgesia·Peter Gabriel PryzbylkowskiLinda Chen

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