NMDA Antagonist Neurotoxicity: Mechanism and Prevention
J. W. Olney, J. Labruyere, G. Wang, D. F. Wozniak, M. T. Price, M. A. Sesma
Science December 6, 1991 DOI: 10.1126/science.1835799 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | anticholinergic drugs diazepam barbiturates |
| Citations | 850 |
| Key findings | The morphological damage to neurons in the rat cerebral cortex caused by NMDA antagonists can be prevented by anticholinergic drugs or by diazepam and barbiturates, which act at the GABA receptor-channel complex. |
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 gamma-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.
Citations in the library
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- Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms Pharmacological Reviews June 26, 2018
- Ketamine Pharmacology: An Update (Pharmacodynamics and Molecular Aspects, Recent Findings) CNS Neuroscience & Therapeutics April 10, 2013
- Ketamine Anesthesia & Analgesia November 1, 1998
- Ketamine: NMDA Receptors and Beyond Journal of Neuroscience November 2, 2016
- NMDA receptor regulation of memory and behavior in humans Hippocampus October 1, 2001
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