Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
2000-04-28
2001-05-29
Henley, III, Raymond (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
Reexamination Certificate
active
06239156
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to the prevention or reduction of glutamate neurotoxicity in the pathophysiology of spinal cord injury induced by aortic crossclamping.
DESCRIPTION OF THE RELATED ART
Spinal cord ischemia remains a devastating complication of thoracoabdominal aortic operations, with paraplegia occurring after as many of 31% of procedures. The cellular and molecular mechanisms that underlie hypoxic-ischemic injury to the spinal cord have not been totally elucidated, but recent studies suggest that the release of excitatory amino acids by ischemic cells into the extracellular space of the central nervous system may contribute substantially to neuronal death.
Glutamate is thought to be the primary excitatory amino acid in the spinal cord, and it may destroy neuronal cells through its actions on N-methyl-D-aspartate (NMDA) and non-NMDA receptors by inducing massive sodium and calcium ion influxes into the cell, resulting in neuronal death. Microdialysis studies have confirmed that an elevation in glutamate level is induced by spinal cord ischemia. Although the neuroprotective effects of NMDA receptor antagonists have been demonstrated both in vitro and in vivo, their pronounced side effects limit their clinical use. Effective NMDA blockers with few side effects have heretofore been unknown.
SUMMARY OF THE INVENTION
The present invention pertains to a method for the reduction of glutamate neurotoxicity in pathophysiology of spinal cord injury induced by aortic cross-clamping. The reduction is achieved by the administration of riluzole to a patient, in an amount effective to reduce glutamate neurotoxicity, contemporaneously with aortic cross-clamping. Preferably, the riluzole is administered both prior to and following the aortic cross-clamping. The method is also applicable to reduce the spinal cord injury resulting from ischemia, and for reducing the effects of ischemia on neuronal tissues.
REFERENCES:
patent: 5624945 (1997-04-01), Bousseau et al.
patent: 5686475 (1997-11-01), Delumeau et al.
patent: 5830907 (1998-11-01), Doble et al.
Heurteaux Catherine
Lang-Lazdunski Loic
Lazdunski Michel
Centre National de la Recherche Scientifique "CNRS"
Henley III Raymond
Schnader Harrison Segal & Lewis LLP
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