Neuronal Degeneration in the Cingulated Gyrus: NMDC Antagonists and Anticholinesterases
Annual rept. 30 SAep 2001-29 Sep 2002
DUKE UNIV MEDICAL CENTER DURHAM NC
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The key objective of these studies is to determine the neurotoxic risk of combining acetylcholinesterase inhibitors AChEIs and N-methyl-D-aspartate NMDA receptor blockers. In this year of study we found 1 The histopathological effect of the non-competitive NMDA antagonist MK-801 is ameliorated by co-exposure to the acetylcholinesterase inhibitor, pyridostigmine bromide in rats however neurotoxicity is exacerbated by Co exposure to the AChEI, physostigmine. 2 The NMDA receptor antagonists dextromethorphan and felbamate do not induce neurotoxicity in exposed animals, nor does co-exposure of these compounds to pyridostigmine bromide induce detectable neurotoxicity. 3 The NMDA receptor antagonist, memantine induces a neurotoxic response visualized by positive Fluoro-Jade-B stain in mature female rats this effect is exacerbated by pyridostigmine bromide. Several animals died with these drug combinations, suggesting this is a toxic combination. 4 The resultant neuropathology in MK-801 and memantine exposed animals is in good agreement with the behavioral deficits exhibited by animals exposed to these compounds. 5 Combined exposure of memantine and PB had a greater effect on IPSPs than did memantine or PB alone.
- Anatomy and Physiology
- Chemical, Biological and Radiological Warfare