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ANESTHETIC PHARMACOLOGY

Contrasting Roles of the N-Methyl-d-Aspartate Receptor in the Production of Immobilization by Conventional and Aromatic Anesthetics

Edmond I. Eger, II, MD^*, Mark Liao, BS^*, Michael J. Laster, DVM^*, Albert Won, MS^*, John Popovich, BS^*, Douglas E. Raines, MD, Ken Solt, MD, Robert C. Dutton, MD^*, Franklin V. Cobos, II, MD, and James M. Sonner, MD^*

Received from the *Department of Anesthesia and Perioperative Care, University of California, San Francisco, California, the Department of Anesthesia and Critical Care, Massachusetts General Hospital and Department of Anaesthesia, Harvard Medical School, Boston Massachusetts, and Department of Anesthesiology, University of Nebraska, Omaha, Nebraska

Address correspondence to Dr. Edmond I Eger II, Department of Anesthesia, S-455, University of California, San Francisco, CA 94143–0464. Address e-mail to egere{at}anesthesia.ucsf.edu.

We hypothesized that N-methyl-d-aspartate (NMDA) receptors mediate some or all of the capacity of inhaled anesthetics to prevent movement in the face of noxious stimulation, and that this capacity to prevent movement correlates directly with the in vitro capacity of such anesthetics to block the NMDA receptor. To test this hypothesis, we measured the effect of IV infusion of the NMDA blockers dizocilpine (MK-801) and (R)-4-(3-phosphonopropyl) piperazine-2-carboxylic acid (CPP) to decrease the MAC (the minimum alveolar concentration of anesthetic that prevents movement in 50% of subjects given a noxious stimulation) of 8 conventional anesthetics (cyclopropane, desflurane, enflurane, halothane, isoflurane, nitrous oxide, sevoflurane, and xenon) and 8 aromatic compounds (benzene, fluorobenzene, o-difluorobenzene, p-difluorobenzene, 1,2,4-trifluorobenzene, 1,3,5-trifluorobenzene, pentafluorobenzene, and hexafluorobenzene) and, for comparison, etomidate. We postulated that MK-801 or CPP infusions would decrease MAC in inverse proportion to the in vitro capacity of these anesthetics to block the NMDA receptor. This notion proved correct for the aromatic inhaled anesthetics, but not for the conventional anesthetics. At the greatest infusion of MK-801 (32 µg · kg^–1· min^–1) the MACs of conventional anesthetics decreased by 59.4 ± 3.4% (mean ± sd) and at 8 µg · kg^–1· min^–1 by 45.5 ± 4.2%, a decrease not significantly different from a 51.4 ± 19.0% decrease produced in the EC₅₀ for etomidate, an anesthetic that acts solely by enhancing -amino butyric acid (GABA) receptors. We conclude that some aromatic anesthetics may produce immobility in the face of noxious stimulation by blocking the action of glutamate on NMDA receptors but that conventional inhaled anesthetics do not.

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999