title: Spinal N-methyl-d-aspartate receptors may contribute to the immobilizing action of isoflurane.
abstract: We examined whether N-methyl-D-aspartate (NMDA) receptors influence the immobilizing effect of isoflurane by a spinal or supraspinal action. We antagonized NMDA receptors by intrathecal (IT), intracerebroventricular (ICV), and IV administration of MK 801 (a noncompetitive NMDA antagonist) and measured the decrease in isoflurane minimum alveolar anesthetic concentration (MAC). We also measured MK 801 tissue concentrations in homogenates of upper and lower spinal cord, a slice of cerebral cortex, and the whole brain. IT infusion of MK 801 decreased isoflurane MAC more potently than ICV or IV infusions. The change in MAC correlated with the MK 801 concentration in the lower part of the spinal cord (P < 0.01) but not with concentrations in supraspinal tissue. The maximal effect of IT MK 801 reached a plateau without achieving anesthesia. IV doses 270-fold larger than the largest IT dose also did not produce anesthesia in the absence of isoflurane. These results suggest that the capacity of MK 801 to decrease the MAC of isoflurane results from an effect on the spinal cord but that spinal NMDA receptors provide only partial mediation of the immobility produced by isoflurane. Because neither IT nor IV MK 801 provide complete anesthesia, these findings also call into question the notion that NMDA blockade alone suffices to produce anesthesia as defined by immobility in the face of noxious stimulation.
  
  
  CONCLUSIONS
  Spinal cord NMDA receptors may mediate a portion of the immobilizing effect of isoflurane. Blockade of NMDA receptors in the cord by MK 801 has a MAC-sparing effect, but MK 801 does not, by itself, produce complete anesthesia.
authors.affiliation: Department of Anesthesia and Perioperative Care, University of California, San Francisco, 94143, USA.
authors.forename: Caroline
authors.initials: C
authors.lastname: Stabernack
authors.forename: James M
authors.initials: JM
authors.lastname: Sonner
authors.forename: Michael
authors.initials: M
authors.lastname: Laster
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yilei
authors.initials: Y
authors.lastname: Xing
authors.forename: Manohar
authors.initials: M
authors.lastname: Sharma
authors.forename: Edmond I
authors.initials: EI
authors.lastname: Eger
mesh_terms: D000465:Algorithms; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D007262:Infusions, Intravenous; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D009068:Movement / Q000187:drug effects*; D011650:Pulmonary Alveoli / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012044:Regression Analysis; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism
chemical_list: D018685:Anesthetics, Inhalation; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D007530:Isoflurane