Lidocaine, MK-801, and MAC

Anesth Analg. 2007 May;104(5):1098-102, tables of contents. doi: 10.1213/01.ane.0000260318.60504.a9.


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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Dizocilpine Maleate / blood
  • Dizocilpine Maleate / pharmacokinetics*
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical / methods
  • Drug Interactions / physiology
  • Lidocaine / blood
  • Lidocaine / pharmacokinetics*
  • Male
  • Rats
  • Rats, Sprague-Dawley


  • Dizocilpine Maleate
  • Lidocaine