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NMDA Antagonist Neurotoxicity: Mechanism and Prevention
Abstract
Antagonists of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor, including phencyclidine (PCP) and ketamine, protect against brain damage in neurological disorders such as stroke. However, these agents have psychotomimetic properties in humans and morphologically damage neurons in the cerebral cortex of rats. It is now shown that the morphological damage can be prevented by certain anticholinergic drugs or by diazepam and barbiturates, which act at the γ-aminobutyric acid (GABA) receptor-channel complex and are known to suppress the psychotomimetic symptoms caused by ketamine. Thus, it may be possible to prevent the unwanted side effects of NMDA antagonists, thereby enhancing their utility as neuroprotective drugs.
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Cited by
Metabolic reduction in the posterior cingulate cortex in very early Alzheimer's disease
Minoshima, S., Giordani, B., Berent, S., Frey, K. A., Foster, N. L., & Kuhl, D. E. (1997) · Annals of Neurology · doi:10.1002/ana.410420114 · Cited by 1,802
Glutamate receptor dysfunction and schizophrenia
Olney, J. W. (1995) · Archives of General Psychiatry · doi:10.1001/archpsyc.1995.03950240016004 · Cited by 1,685
Self-citationJentsch, J. (1999) · Neuropsychopharmacology · doi:10.1016/s0893-133x(98)00060-8 · Cited by 1,314
Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms
Zanos, P., Moaddel, R., Morris, P. J., Riggs, L. M., Highland, J. N., Georgiou, P., Pereira, E. F. R., Albuquerque, E. X., Thomas, C. J., Zarate, C. A., et al. (2018) · Pharmacological Reviews · doi:10.1124/pr.117.015198 · Cited by 1,260
Excitotoxicity and stroke: Identifying novel targets for neuroprotection
Lai, T. W., Zhang, S., & Wang, Y. T. (2014) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2013.11.006 · Cited by 1,106
Metadata
- Authors
- Olney, J. W., Labruyere, J., Wang, G., Wozniak, D. F., Price, M. T., & Sesma, M. A.
- Venue
- Science
- Published
- 1991-12-06
- Volume
- 254
- Issue
- 5037
- Pages
- 1515-1518
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2021099633
- Cited by
- 841
- References
- 0
- FWCI
- 9.50
- Type
- journal article
- Language
- en
- Open access
- closed
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- Olney, J. W., Labruyere, J., Wang, G., Wozniak, D. F., Price, M. T., & Sesma, M. A. (1991). NMDA Antagonist Neurotoxicity: Mechanism and Prevention. Science. https://doi.org/10.1126/science.1835799
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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