Accession Number:

ADA415832

Title:

Neuronal Degeneration in the Cingulated Gyrus: NMDC Antagonists and Anticholinesterases

Descriptive Note:

Annual rept. 30 SAep 2001-29 Sep 2002

Corporate Author:

DUKE UNIV MEDICAL CENTER DURHAM NC

Report Date:

2002-10-01

Pagination or Media Count:

82.0

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.

Subject Categories:

  • Biochemistry
  • Anatomy and Physiology
  • Chemical, Biological and Radiological Warfare

Distribution Statement:

APPROVED FOR PUBLIC RELEASE