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ANESTHETIC PHARMACOLOGY

Lidocaine, MK-801, and MAC

Yi Zhang, MD, Michael J. Laster, DVM^*, Edmond I. Eger, II, MD^*, Manohar Sharma, PhD^*, and James M. Sonner, MD^*

From the *Department of Anesthesia and Perioperative Care, University of California, San Francisco, California, and from the Department of Anesthesiology, Fuwai Hospital and Cardiovascular Institute, Beijing, China.

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

BACKGROUND: Previous studies have found that the local anesthetic/sodium channel blocker lidocaine decreased MAC by maximum amounts approximately equal to the decreases produced by dizocilpine (MK-801), a N-methyl-d-aspartate (NMDA) receptor antagonist. Blockade of sodium channels by inhaled anesthetics has been suggested as a possible cause for impairment of transmission through NMDA receptors. We postulated that the net effect of lidocaine and MK-801 on MAC would be the same, albeit by affecting NMDA neurotransmission at different points.

METHODS: We measured the effect of various lidocaine infusions on the MAC of cyclopropane, halothane, isoflurane, and o-difluorobenzene in rats. We also measured the effect of concurrent lidocaine-MK-801 infusion on the MAC of isoflurane and o-difluorobenzene.

RESULTS: Our data contradicted our predictions. (a) We found no limit to the effect of lidocaine infusion, in some cases finding that lidocaine, alone, produced immobility; (b) lidocaine infusion did not decrease the MAC of o-difluorobenzene differently from the MAC of other inhaled anesthetics; and (c) the addition of MK-801 equally affected the decrease in MAC produced by lidocaine infusion for isoflurane versus o-difluorobenzene.

CONCLUSION: Lidocaine does not primarily decrease MAC by decreasing the release of glutamate from nerve terminals.

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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