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NPS 1506 attenuates cognitive dysfunction and hippocampal neuron death following brain trauma in the rat.

Abstract
Although several noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonists have been shown to be substantially efficacious in experimental models of brain trauma, side effects associated with this class of compounds have impeded clinical application. Therefore, new noncompetitive NMDA receptor antagonists have been developed, including NPS 1506, that appear to be nontoxic but retain efficacy. In the present study, we evaluated the efficacy of NPS 1506 in a model of parasagittal fluid percussion brain trauma in the anesthetized rat. Administration of 1 mg/kg NPS 1506 at both 10 min and 4 h posttrauma induced no changes in brain temperature, mean arterial pressure, pulse, or arterial blood gasses. At 1 week postinjury, animals treated with the same dosing regimen of NPS 1506 demonstrated a dramatic attenuation of memory dysfunction evaluated by a water maze task (P < 0.02) and had greatly reduced neuron death in the CA3 subfield of the hippocampus (P < 0.01). However, NPS 1506 treatment did not significantly affect the extent of cortical tissue loss following injury. Since memory dysfunction and hippocampal damage are common and potentially related consequences of brain trauma in humans, our results suggest that NPS 1506 treatment may have clinical utility.
AuthorsM J Leoni, X H Chen, A L Mueller, J Cheney, T K McIntosh, D H Smith
JournalExperimental neurology (Exp Neurol) Vol. 166 Issue 2 Pg. 442-9 (Dec 2000) ISSN: 0014-4886 [Print] United States
PMID11085909 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
CopyrightCopyright 2000 Academic Press.
Chemical References
  • Fluorobenzenes
  • Neuroprotective Agents
  • Receptors, N-Methyl-D-Aspartate
  • NPS 1506
Topics
  • Animals
  • Brain Injuries (drug therapy, pathology)
  • Cell Death (drug effects)
  • Cognition (drug effects)
  • Fluorobenzenes (pharmacology)
  • Hippocampus (pathology)
  • Male
  • Maze Learning (drug effects)
  • Memory Disorders (drug therapy, pathology)
  • Neuroprotective Agents (pharmacology)
  • Pyramidal Cells (pathology)
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate (antagonists & inhibitors)

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