Neuronal Degeneration in the Cingulated Gyrus: NMDC Antagonists and Anticholinesterases
Abstract
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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2002
- Accession Number
- ADA415832
Entities
People
- Katherine Jones
- Qiang Li
- Wilkie A. Wilson
Organizations
- Duke University Hospital