NMDA antagonist neurotoxicity: Mechanism and prevention

J. W. Olney, J. Labruyere, G. Wang, D. F. Wozniak, M. T. Price, M. A. Sesma

Research output: Contribution to journalArticlepeer-review

729 Scopus citations

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.

Original languageEnglish
Pages (from-to)1515-1518
Number of pages4
JournalScience
Volume254
Issue number5037
DOIs
StatePublished - 1991

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