NMDA Antagonist Neurotoxicity: Mechanism and Prevention
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 c...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 1991-12, Vol.254 (5037), p.1515-1518 |
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| container_title | Science (American Association for the Advancement of Science) |
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| creator | Olney, J. W. Labruyere, J. Wang, G. Wozniak, D. F. Price, M. T. Sesma, M. A. |
| description | 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. |
| doi_str_mv | 10.1126/science.1835799 |
| format | Article |
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Thus, it may be possible to prevent the unwanted side effects of NMDA antagonists, thereby enhancing their utility as neuroprotective drugs.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.1835799</identifier><identifier>PMID: 1835799</identifier><identifier>CODEN: SCIEAS</identifier><language>eng</language><publisher>United States: American Society for the Advancement of Science</publisher><subject>Animals ; Anticholinergics ; Barbiturates ; Barbiturates - pharmacology ; Chick Embryo ; Dizocilpine Maleate - antagonists & inhibitors ; Dosage ; Drugs ; Excitatory amino acids ; GABA antagonists ; Histology ; Methyl aspartate ; N-methyl-D-aspartate ; Neurological disorders ; Neurons ; Neurotoxicity ; Neurotoxins - antagonists & inhibitors ; Neurotransmitter receptors ; Parasympatholytics - pharmacology ; Physiological aspects ; Pilocarpine - pharmacology ; Rats ; Receptors ; Receptors, N-Methyl-D-Aspartate - drug effects ; Scopolamine - pharmacology ; Side effects ; Stroke ; Stroke (Disease) ; Vacuoles ; Vacuoles - ultrastructure</subject><ispartof>Science (American Association for the Advancement of Science), 1991-12, Vol.254 (5037), p.1515-1518</ispartof><rights>Copyright 1991 American Association for the Advancement of Science</rights><rights>COPYRIGHT 1991 American Association for the Advancement of Science</rights><rights>COPYRIGHT 1991 American Association for the Advancement of Science</rights><rights>Copyright American Association for the Advancement of Science Dec 6, 1991</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c776t-9d1eab3874dbdea0ad700bb1bd9eedcfa2f875ac3168eb74f631dd11b7cb96db3</citedby><cites>FETCH-LOGICAL-c776t-9d1eab3874dbdea0ad700bb1bd9eedcfa2f875ac3168eb74f631dd11b7cb96db3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/2879444$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/2879444$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>314,776,780,799,2871,2872,27901,27902,57992,58225</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1835799$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Olney, J. 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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.</abstract><cop>United States</cop><pub>American Society for the Advancement of Science</pub><pmid>1835799</pmid><doi>10.1126/science.1835799</doi><tpages>4</tpages></addata></record> |
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| ispartof | Science (American Association for the Advancement of Science), 1991-12, Vol.254 (5037), p.1515-1518 |
| issn | 0036-8075 1095-9203 |
| language | eng |
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| source | American Association for the Advancement of Science; Jstor Complete Legacy; MEDLINE |
| subjects | Animals Anticholinergics Barbiturates Barbiturates - pharmacology Chick Embryo Dizocilpine Maleate - antagonists & inhibitors Dosage Drugs Excitatory amino acids GABA antagonists Histology Methyl aspartate N-methyl-D-aspartate Neurological disorders Neurons Neurotoxicity Neurotoxins - antagonists & inhibitors Neurotransmitter receptors Parasympatholytics - pharmacology Physiological aspects Pilocarpine - pharmacology Rats Receptors Receptors, N-Methyl-D-Aspartate - drug effects Scopolamine - pharmacology Side effects Stroke Stroke (Disease) Vacuoles Vacuoles - ultrastructure |
| title | NMDA Antagonist Neurotoxicity: Mechanism and Prevention |
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