Comparison of the neuroprotective effects of the N-methyl-D-aspartate antagonist MK-801 and the opiate-receptor antagonist nalmefene in experimental spinal cord ischemia
S. W. Yum and A. I. Faden
Department of Neurology, University of California, San Francisco.
Both N-methyl-D-aspartate (NMDA)-receptor antagonists and opiate-receptor
antagonists have been shown to limit tissue damage after ischemic central
nervous system injury. We compared the neuroprotective effects of the
noncompetitive NMDA-receptor antagonist MK-801 and the opiate-receptor
antagonist nalmefene in a model of global spinal cord ischemia and
reperfusion in unanesthetized rabbits. MK-801 (1 mg/kg) or nalmefene (0.1
mg/kg) was administered intravenously 5 minutes after reperfusion. MK-801
treatment and nalmefene treatment each significantly improved the
neurologic and histologic outcome compared with saline controls.
Differences in these outcome measures between MK-801 treatment and
nalmefene treatment did not reach statistical significance. Our results are
consistent with the hypothesis that multiple factors, including endogenous
opioids and excitatory amino acids, contribute to the secondary tissue
injury after central nervous system ischemia. These data also provide
further evidence that therapeutic interventions with opiate-receptor
antagonists or NMDA antagonists may be beneficial in limiting neurologic
dysfunction after ischemic brain or spinal cord injury.
