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Science 6 December 1991:
Vol. 254. no. 5037, pp. 1515 - 1518
DOI: 10.1126/science.1835799
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Articles

Science, Vol 254, Issue 5037, 1515-1518
Copyright © 1991 by American Association for the Advancement of Science

articles

NMDA antagonist neurotoxicity: mechanism and prevention

JW Olney, J Labruyere, G Wang, DF Wozniak, MT Price, and MA Sesma

Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110.

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.


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Science. ISSN 0036-8075 (print), 1095-9203 (online)