Lidocaine, MK-801, and MAC.

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.

Rapid quantification of the non-competitive NMDA antagonist MK-801 in canine cerebrospinal fluid and plasma by capillary gas chromatography-nitrogen phosphorus detection.

A facile and sensitive method utilizing solid-phase cartridge extraction and capillary gas chromatography (GC) with nitrogen phosphorus detection was validated for the determination of MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclo-hepten-5,10-imine maleate], a non-competitive NMDA receptor antagonist, in dog cerebrospinal fluid (CSF) and plasma. Clonidine hydrochloride was used as the internal standard (ISTD), after evaluation of several ISTD candidates. Separations were performed with an intermediate polarity fused silica capillary column, yielding typical retention times of 3.20 min for MK-801 and 4.90 min for ISTD. Plasma and CSF samples were extracted with 100 mg Bond Elut C(18) TCA Copyright cartridges to yield methanolic eluates that were evaporatively enriched before reconstitution in anhydrous ethanol prior to injection. The standard curve was validated from 1 to 100,000 ng/ml for CSF, and from 0.1 to 1,000 ng/ml for plasma. Chromatograms from naive plasma and CSF exhibited no endogenous interfering peaks. The efficiency of extraction recovery was >94%, and the intra-assay and inter-assay precision was within 9% relative standard deviation (%R.S.D.) for both fluids. MK-801 and ISTD were stable in the injection solvent at 22 degrees C for at least 48 h. The assay was applied to the toxocologic study of intrathecal MK-801 administration in the dog.