Neuroscience 2005 Abstract
| Presentation Number: | 106.4 |
|---|---|
| Abstract Title: | Memantine neurotoxicity and lethal interactions with acetylcholinesterase inhibitors (AChEIs). |
| Authors: |
Jones, K. H.*1
; Clark, S.4
; Guo-Ross, S. X.5
; Zaman, V.6
; Kuhn, E.2
; Swartzwelder, H. S.3
; Wilson, W. A.1
1Pharmacology and Cancer Biology, Duke Univ. Med. Ctr., Durham, NC 2Neurobiology, Duke Univ. Med. Ctr., Durham, NC 3Psychiatry, Duke Univ. Med. Ctr., Durham, NC 4CO, 508 Fulton St., 27705, 5USA, 508 Fulton St., 27705, 6Col. Veterinary Med. and Biomed. Sci, 508 Fulton St., 27705, |
| Primary Theme and Topics |
Disorders of the Nervous System - Neurotoxicity, Inflammation, and Neuroprotection -- Toxic metabolic effects and disorders |
| Session: |
106. Toxic and Metabolic Disorders: Animal Models Poster |
| Presentation Time: | Saturday, November 12, 2005 4:00 PM-5:00 PM |
| Location: | Washington Convention Center - Hall A-C, Board # UU45 |
| Keywords: | memantine, neurotoxicity, acetylcholinesterase inhibitors, Fluoro-jade B |
N-methyl-D-aspartate (NMDA) antagonists have been investigated for therapeutic potential for a variety of neurological disorders. However, many NMDA antagonists produce undesirable psychotropic side effects in humans and neurotoxic effects in animals. In addition, NMDA antagonist-mediated neurotoxicity in the rat is exacerbated by co-exposure to cholinergic agonists. Olney, et al. (2004 SFN abstract 219.6) recently reported that anti-Alzheimer’s AChEI's exacerbate NMDA antagonist neurotoxicity. We assessed the neurotoxicity of four NMDA antagonists (MK-801, dextromethorphan, felbamate, or memantine) combined with two AChEIs (pyridostigmine and physostigmine) in adult female rats. Toxicity was assessed using Fluoro-Jade B (FJ-B) staining in the posterior cingulate and retrosplenial corticies (PC/RSC), areas highly sensitive to this toxicity. Memantine (25 mg/kg) was unexpectedly neurotoxic. For all NMDA antagonists, neither AChEI increased FJ-B staining. However, memantine and dextromethorphan were unexpectedly lethal when used in combination with pyridostigmine. These data suggest caution should be used when combining certain agents of these two classes of compounds, and also suggest that memantine produces neurodegeneration in important areas of the rat brain.
Supported by Department of Defense (Neurotoxin Exposure Treatment
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2005 Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience, 2005. Online.
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