{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T01:37:42Z","timestamp":1791164262278,"version":"4.1.0"},"reference-count":25,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5037","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[1991,12,6]]},"abstract":"<jats:p>Antagonists of the<jats:italic>N<\/jats:italic>-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 \u03b3-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.<\/jats:p>","DOI":"10.1126\/science.1835799","type":"journal-article","created":{"date-parts":[[2006,10,5]],"date-time":"2006-10-05T22:10:16Z","timestamp":1160086216000},"page":"1515-1518","source":"Crossref","is-referenced-by-count":703,"title":["NMDA Antagonist Neurotoxicity: Mechanism and Prevention"],"prefix":"10.1126","volume":"254","author":[{"given":"J. W.","family":"Olney","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Labruyere","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. F.","family":"Wozniak","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. T.","family":"Price","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. A.","family":"Sesma","sequence":"additional","affiliation":[{"name":"School of Optometry, University of Missouri- St. Louis, St. Louis, MO 63110."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_2_1_1_1","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1113\/jphysiol.1987.sp016861","volume":"394","year":"1987","unstructured":"AKAIKE, N, KINETIC-PROPERTIES OF THE PENTOBARBITAL-GATED CHLORIDE CURRENT IN FROG SENSORY NEURONS, JOURNAL OF PHYSIOLOGY-LONDON 394: 85 (1987).","journal-title":"JOURNAL OF PHYSIOLOGY-LONDON"},{"key":"e_1_2_1_2_1","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1126\/science.247.4939.221.b","volume":"247","year":"1990","unstructured":"ALLEN, H.L., PHENCYCLIDINE, DIZOCILPINE, AND CEREBROCORTICAL NEURONS, SCIENCE 247: 221 (1990).","journal-title":"SCIENCE"},{"key":"e_1_2_1_3_1","first-page":"377","volume":"53","year":"1976","unstructured":"AYIM, E.N., EFFECTS OF DIAZEPAM ON KETAMINE ANESTHESIA, EAST AFRICAN MEDICAL JOURNAL 53: 377 (1976).","journal-title":"EAST AFRICAN MEDICAL JOURNAL"},{"key":"e_1_2_1_4_1","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1002\/mds.870010208","volume":"1","year":"1986","unstructured":"BURKE, R.E., MOVEMENT DISORDERS 1: 135 (1986).","journal-title":"MOVEMENT DISORDERS"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(88)90162-6"},{"key":"e_1_2_1_6_1","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1111\/j.1365-2044.1973.tb00449.x","volume":"28","year":"1973","unstructured":"COPPEL, D.L., TAMING OF KETAMINE, ANAESTHESIA 28: 293 (1973).","journal-title":"ANAESTHESIA"},{"key":"e_1_2_1_7_1","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/0014-2999(88)90155-0","volume":"156","year":"1988","unstructured":"FREEDMAN, S.B., MUSCARINIC M1, M2 RECEPTOR-BINDING - RELATIONSHIP WITH FUNCTIONAL EFFICACY, EUROPEAN JOURNAL OF PHARMACOLOGY 156: 133 (1988).","journal-title":"EUROPEAN JOURNAL OF PHARMACOLOGY"},{"key":"e_1_2_1_8_1","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1111\/j.1399-6576.1978.tb01348.x","volume":"22","year":"1978","unstructured":"KORTTILA, K, UNTOWARD EFFECTS OF KETAMINE COMBINED WITH DIAZEPAM FOR SUPPLEMENTING CONDUCTION ANESTHESIA IN YOUNG AND MIDDLE-AGED ADULTS, ACTA ANAESTHESIOLOGICA SCANDINAVICA 22: 640 (1978).","journal-title":"ACTA ANAESTHESIOLOGICA SCANDINAVICA"},{"key":"e_1_2_1_9_1","first-page":"761","volume":"15","year":"1989","unstructured":"LABRUYERE, J, SOCIETY FOR NEUROSCIENCE. ABSTRACTS 15: 761 (1989).","journal-title":"SOCIETY FOR NEUROSCIENCE. ABSTRACTS"},{"key":"e_1_2_1_10_1","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1016\/0896-6273(88)90125-0","volume":"1","year":"1988","unstructured":"LEVITAN, E.S., BIOPHYSICAL AND PHARMACOLOGICAL PROPERTIES OF CLONED GABAA RECEPTOR SUBUNITS EXPRESSED IN XENOPUS OOCYTES, NEURON 1: 773 (1988).","journal-title":"NEURON"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.205953"},{"key":"e_1_2_1_12_1","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1007\/BF03005737","volume":"21","year":"1974","unstructured":"MAGBAGBEOLA, JAO, CANADIAN ANAESTHETISTS SOCIETY JOURNAL 21: 321 (1974).","journal-title":"CANADIAN ANAESTHETISTS SOCIETY JOURNAL"},{"key":"e_1_2_1_13_1","first-page":"307","year":"1990","unstructured":"Marshall, B. E., Goodman and Gilman's The Pharmacological Basis of Therapeutics: 307 (1990).","journal-title":"Goodman and Gilman's The Pharmacological Basis of Therapeutics"},{"key":"e_1_2_1_14_1","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/0006-3223(89)90072-3","volume":"26","year":"1989","unstructured":"OLNEY, J.W., EXCITATORY AMINO-ACIDS AND NEUROPSYCHIATRIC DISORDERS, BIOLOGICAL PSYCHIATRY 26: 505 (1989).","journal-title":"BIOLOGICAL PSYCHIATRY"},{"key":"e_1_2_1_15_1","first-page":"337","year":"1988","unstructured":"Olney, J. W., Excitatory Amino Acids in Health and Disease: 337 (1988).","journal-title":"Excitatory Amino Acids in Health and Disease"},{"key":"e_1_2_1_16_1","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/0304-3940(86)90224-7","volume":"68","year":"1986","unstructured":"OLNEY, J.W., THE ANTI-EXCITOTOXIC EFFECTS OF CERTAIN ANESTHETICS, ANALGESICS AND SEDATIVE-HYPNOTICS, NEUROSCIENCE LETTERS 68: 29 (1986).","journal-title":"NEUROSCIENCE LETTERS"},{"key":"e_1_2_1_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2660263"},{"key":"e_1_2_1_18_1","unstructured":"OLNEY J.W. unpublished data."},{"key":"e_1_2_1_19_1","unstructured":"Paxinos G. The Rat Brain in Stereotaxic Coordinates (1982)."},{"key":"e_1_2_1_20_1","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1007\/BF03011442","volume":"36","year":"1989","unstructured":"REICH, D.L., CANADIAN JOURNAL OF ANAESTHESIA-JOURNAL CANADIEN D ANESTHESIE 36: 186 (1989).","journal-title":"CANADIAN JOURNAL OF ANAESTHESIA-JOURNAL CANADIEN D ANESTHESIE"},{"key":"e_1_2_1_21_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.04-07-01884.1984"},{"key":"e_1_2_1_22_1","unstructured":"Sesma M. A. Soc. Neurosci. Abstr. in press."},{"key":"e_1_2_1_23_1","first-page":"1122","volume":"16","year":"1990","unstructured":"SHARP, J.W., SOCIETY FOR NEUROSCIENCE. ABSTRACTS 16: 1122 (1990).","journal-title":"SOCIETY FOR NEUROSCIENCE. ABSTRACTS"},{"key":"e_1_2_1_24_1","first-page":"7180","volume":"78","year":"1981","unstructured":"Study, R. E., Proceedings of the National Academy of Sciences of the United States of America 78: 7180 (1981).","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"e_1_2_1_25_1","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1176\/ajp.148.2.162","volume":"148","year":"1991","unstructured":"ZORUMSKI, C.F., INSIGHTS INTO THE STRUCTURE AND FUNCTION OF GABA-BENZODIAZEPINE RECEPTORS - ION CHANNELS AND PSYCHIATRY, AMERICAN JOURNAL OF PSYCHIATRY 148: 162 (1991).","journal-title":"AMERICAN JOURNAL OF PSYCHIATRY"}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.1835799","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,11]],"date-time":"2025-01-11T08:21:13Z","timestamp":1736583673000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.1835799"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1991,12,6]]},"references-count":25,"journal-issue":{"issue":"5037","published-print":{"date-parts":[[1991,12,6]]}},"alternative-id":["10.1126\/science.1835799"],"URL":"https:\/\/doi.org\/10.1126\/science.1835799","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[1991,12,6]]}}}