Evaluation of glycine site antagonists of the NMDA receptor in global cerebral ischaemia
In the present studies we have investigated the effects of a range of glycine site antagonists of the N-methyl- d-aspartate (NMDA) receptor in the gerbil model of global cerebral ischaemia. The compounds tested were (+)-3-amino-1-hydroxy-2-pyrrolidone (HA 966, 15 mg/kg), 7-chloro-4-hydroxy-3-(3-phen...
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| creator | Hicks, Caroline A. Ward, Mark A. Ragumoorthy, Nella Ambler, Samantha J. Dell, Colin P. Dobson, David O'Neill, Michael J. |
| description | In the present studies we have investigated the effects of a range of glycine site antagonists of the
N-methyl-
d-aspartate (NMDA) receptor in the gerbil model of global cerebral ischaemia. The compounds tested were (+)-3-amino-1-hydroxy-2-pyrrolidone (HA 966, 15 mg/kg), 7-chloro-4-hydroxy-3-(3-phenoxy)phenyl-2(
H)-quinolinone) (L-701,324, 40 mg/kg), 7-chloro-3-(cyclopropylcarbonyl)-4-hydroxy-2(1
H)-quinolinone) (L-701,252, 50 mg/kg), (3-(3-hydroxyphenyl)prop-2-ynyl 7-chloro-4 hydroxy-2(1
H)-quinolone-3-carboxylate) (L-701,273, 50 mg/kg), 5-nitro-6,7-dichloro-2,3-quinoxalinedione (ACEA 1021, 25 mg/kg) and [(
E)-3[(phenylcarbamoyl) ethenyl]-4,6-dichloroindole-2-carboxylic acid sodium salt (GV 150526A, 40 mg/kg). All compounds were administered via the i.p. route 30 min before and again at 2 h 30 min after 5 min bilateral carotid artery occlusion (BCAO) in the gerbil. For comparison we also evaluated a non-competitive NMDA antagonist, (5
R,10
S)-(+)-5-methyl-10,11-dihydro-5
H-dibenzo[
a,
d]cyclohepten-5,10-imine (MK-801, 2 mg/kg) and an α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) antagonist, (3
S,4a
R, 6
R, 8a
R)-6-[2-(1(2)
H-tetrazole-5-yl)]decahydroisoquinoline-3-carboxylic acid (LY293558, 20 mg/kg). In the present studies L-701,252, L-701,324 and L-701,273 provided a small degree of neuroprotection. ACEA 1021, GV 150526A and HA 966 failed to provide any neuroprotection, while MK-801 provided significant (20%) protection. In contrast LY293558 provided good (55%) neuroprotection. These results indicate that glycine site antagonists and competitive NMDA antagonists provide a small degree of neuroprotection in global cerebral ischaemia. In contrast, AMPA receptor antagonists provide more robust neuroprotection in global cerebral ischaemia. |
| doi_str_mv | 10.1016/S0006-8993(98)01329-8 |
| format | Article |
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N-methyl-
d-aspartate (NMDA) receptor in the gerbil model of global cerebral ischaemia. The compounds tested were (+)-3-amino-1-hydroxy-2-pyrrolidone (HA 966, 15 mg/kg), 7-chloro-4-hydroxy-3-(3-phenoxy)phenyl-2(
H)-quinolinone) (L-701,324, 40 mg/kg), 7-chloro-3-(cyclopropylcarbonyl)-4-hydroxy-2(1
H)-quinolinone) (L-701,252, 50 mg/kg), (3-(3-hydroxyphenyl)prop-2-ynyl 7-chloro-4 hydroxy-2(1
H)-quinolone-3-carboxylate) (L-701,273, 50 mg/kg), 5-nitro-6,7-dichloro-2,3-quinoxalinedione (ACEA 1021, 25 mg/kg) and [(
E)-3[(phenylcarbamoyl) ethenyl]-4,6-dichloroindole-2-carboxylic acid sodium salt (GV 150526A, 40 mg/kg). All compounds were administered via the i.p. route 30 min before and again at 2 h 30 min after 5 min bilateral carotid artery occlusion (BCAO) in the gerbil. For comparison we also evaluated a non-competitive NMDA antagonist, (5
R,10
S)-(+)-5-methyl-10,11-dihydro-5
H-dibenzo[
a,
d]cyclohepten-5,10-imine (MK-801, 2 mg/kg) and an α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) antagonist, (3
S,4a
R, 6
R, 8a
R)-6-[2-(1(2)
H-tetrazole-5-yl)]decahydroisoquinoline-3-carboxylic acid (LY293558, 20 mg/kg). In the present studies L-701,252, L-701,324 and L-701,273 provided a small degree of neuroprotection. ACEA 1021, GV 150526A and HA 966 failed to provide any neuroprotection, while MK-801 provided significant (20%) protection. In contrast LY293558 provided good (55%) neuroprotection. These results indicate that glycine site antagonists and competitive NMDA antagonists provide a small degree of neuroprotection in global cerebral ischaemia. In contrast, AMPA receptor antagonists provide more robust neuroprotection in global cerebral ischaemia.</description><identifier>ISSN: 0006-8993</identifier><identifier>EISSN: 1872-6240</identifier><identifier>DOI: 10.1016/S0006-8993(98)01329-8</identifier><identifier>PMID: 10082862</identifier><identifier>CODEN: BRREAP</identifier><language>eng</language><publisher>London: Elsevier B.V</publisher><subject>ACEA1021 ; Animals ; Arterial Occlusive Diseases - complications ; Biological and medical sciences ; Carotid Artery Diseases - complications ; Cell Death - drug effects ; Cerebral ischaemia ; Excitatory Amino Acid Antagonists - pharmacology ; Gerbil ; Gerbillinae ; Glycine site antagonist ; GV150526A ; Hippocampus - drug effects ; Hippocampus - metabolism ; Ischemic Attack, Transient - drug therapy ; Ischemic Attack, Transient - etiology ; Ischemic Attack, Transient - pathology ; L-701 ; LY293558 ; Male ; Medical sciences ; Neurology ; Neurons - drug effects ; Neurons - metabolism ; Neuroprotection ; Neuroprotective Agents - pharmacology ; Receptors, AMPA - antagonists & inhibitors ; Receptors, Glycine - antagonists & inhibitors ; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors ; Vascular diseases and vascular malformations of the nervous system</subject><ispartof>Brain research, 1999-02, Vol.819 (1), p.65-74</ispartof><rights>1999 Elsevier Science B.V.</rights><rights>1999 INIST-CNRS</rights><rights>Copyright 1999 Elsevier Science B.V.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c487t-da4c7de0a7039845c2ea8270de370a86df9cf9a555f242210d8626652c0d5e483</citedby><cites>FETCH-LOGICAL-c487t-da4c7de0a7039845c2ea8270de370a86df9cf9a555f242210d8626652c0d5e483</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0006-8993(98)01329-8$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,45974</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1676514$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10082862$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hicks, Caroline A.</creatorcontrib><creatorcontrib>Ward, Mark A.</creatorcontrib><creatorcontrib>Ragumoorthy, Nella</creatorcontrib><creatorcontrib>Ambler, Samantha J.</creatorcontrib><creatorcontrib>Dell, Colin P.</creatorcontrib><creatorcontrib>Dobson, David</creatorcontrib><creatorcontrib>O'Neill, Michael J.</creatorcontrib><title>Evaluation of glycine site antagonists of the NMDA receptor in global cerebral ischaemia</title><title>Brain research</title><addtitle>Brain Res</addtitle><description>In the present studies we have investigated the effects of a range of glycine site antagonists of the
N-methyl-
d-aspartate (NMDA) receptor in the gerbil model of global cerebral ischaemia. The compounds tested were (+)-3-amino-1-hydroxy-2-pyrrolidone (HA 966, 15 mg/kg), 7-chloro-4-hydroxy-3-(3-phenoxy)phenyl-2(
H)-quinolinone) (L-701,324, 40 mg/kg), 7-chloro-3-(cyclopropylcarbonyl)-4-hydroxy-2(1
H)-quinolinone) (L-701,252, 50 mg/kg), (3-(3-hydroxyphenyl)prop-2-ynyl 7-chloro-4 hydroxy-2(1
H)-quinolone-3-carboxylate) (L-701,273, 50 mg/kg), 5-nitro-6,7-dichloro-2,3-quinoxalinedione (ACEA 1021, 25 mg/kg) and [(
E)-3[(phenylcarbamoyl) ethenyl]-4,6-dichloroindole-2-carboxylic acid sodium salt (GV 150526A, 40 mg/kg). All compounds were administered via the i.p. route 30 min before and again at 2 h 30 min after 5 min bilateral carotid artery occlusion (BCAO) in the gerbil. For comparison we also evaluated a non-competitive NMDA antagonist, (5
R,10
S)-(+)-5-methyl-10,11-dihydro-5
H-dibenzo[
a,
d]cyclohepten-5,10-imine (MK-801, 2 mg/kg) and an α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) antagonist, (3
S,4a
R, 6
R, 8a
R)-6-[2-(1(2)
H-tetrazole-5-yl)]decahydroisoquinoline-3-carboxylic acid (LY293558, 20 mg/kg). In the present studies L-701,252, L-701,324 and L-701,273 provided a small degree of neuroprotection. ACEA 1021, GV 150526A and HA 966 failed to provide any neuroprotection, while MK-801 provided significant (20%) protection. In contrast LY293558 provided good (55%) neuroprotection. These results indicate that glycine site antagonists and competitive NMDA antagonists provide a small degree of neuroprotection in global cerebral ischaemia. In contrast, AMPA receptor antagonists provide more robust neuroprotection in global cerebral ischaemia.</description><subject>ACEA1021</subject><subject>Animals</subject><subject>Arterial Occlusive Diseases - complications</subject><subject>Biological and medical sciences</subject><subject>Carotid Artery Diseases - complications</subject><subject>Cell Death - drug effects</subject><subject>Cerebral ischaemia</subject><subject>Excitatory Amino Acid Antagonists - pharmacology</subject><subject>Gerbil</subject><subject>Gerbillinae</subject><subject>Glycine site antagonist</subject><subject>GV150526A</subject><subject>Hippocampus - drug effects</subject><subject>Hippocampus - metabolism</subject><subject>Ischemic Attack, Transient - drug therapy</subject><subject>Ischemic Attack, Transient - etiology</subject><subject>Ischemic Attack, Transient - pathology</subject><subject>L-701</subject><subject>LY293558</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Neurology</subject><subject>Neurons - drug effects</subject><subject>Neurons - metabolism</subject><subject>Neuroprotection</subject><subject>Neuroprotective Agents - pharmacology</subject><subject>Receptors, AMPA - antagonists & inhibitors</subject><subject>Receptors, Glycine - antagonists & inhibitors</subject><subject>Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors</subject><subject>Vascular diseases and vascular malformations of the nervous system</subject><issn>0006-8993</issn><issn>1872-6240</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1PFDEYgBsCkXX1J2jmQIwcBvsx7bQnQxCBBPWgJtyad9t3oGZ2urZdEv69XXYD3ji1TZ-3ffIQ8o7RE0aZ-vSTUqpabYz4aPQxZYKbVu-RGdM9bxXv6D6ZPSGH5HXOf-pRCENfkUNGqeZa8Rm5Ob-HcQ0lxKmJQ3M7PrgwYZNDwQamArdxCrnkzV25w-b7ty-nTUKHqxJTE6Y6EBcwNg4TLlLdhOzuAJcB3pCDAcaMb3frnPz-ev7r7LK9_nFxdXZ63bpO96X10LneI4WeCqM76TiC5j31KHoKWvnBuMGAlHLgHeeM-qqtlOSOeomdFnPyYfvuKsW_a8zFLqsDjiNMGNfZKqOE7Jh8EWQ96wTTvIJyC7oUc0442FUKS0gPllG7aW8f29tNWGu0fWxvNybvdx-sF0v0_01tY1fgaAdAdjAOCSYX8jOneiWrw5x83mJYs90HTDa7gJNDH2r5Yn0ML5j8A4Gkn40</recordid><startdate>19990220</startdate><enddate>19990220</enddate><creator>Hicks, Caroline A.</creator><creator>Ward, Mark A.</creator><creator>Ragumoorthy, Nella</creator><creator>Ambler, Samantha J.</creator><creator>Dell, Colin P.</creator><creator>Dobson, David</creator><creator>O'Neill, Michael J.</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7X8</scope></search><sort><creationdate>19990220</creationdate><title>Evaluation of glycine site antagonists of the NMDA receptor in global cerebral ischaemia</title><author>Hicks, Caroline A. ; Ward, Mark A. ; Ragumoorthy, Nella ; Ambler, Samantha J. ; Dell, Colin P. ; Dobson, David ; O'Neill, Michael J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c487t-da4c7de0a7039845c2ea8270de370a86df9cf9a555f242210d8626652c0d5e483</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>ACEA1021</topic><topic>Animals</topic><topic>Arterial Occlusive Diseases - complications</topic><topic>Biological and medical sciences</topic><topic>Carotid Artery Diseases - complications</topic><topic>Cell Death - drug effects</topic><topic>Cerebral ischaemia</topic><topic>Excitatory Amino Acid Antagonists - pharmacology</topic><topic>Gerbil</topic><topic>Gerbillinae</topic><topic>Glycine site antagonist</topic><topic>GV150526A</topic><topic>Hippocampus - drug effects</topic><topic>Hippocampus - metabolism</topic><topic>Ischemic Attack, Transient - drug therapy</topic><topic>Ischemic Attack, Transient - etiology</topic><topic>Ischemic Attack, Transient - pathology</topic><topic>L-701</topic><topic>LY293558</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Neurology</topic><topic>Neurons - drug effects</topic><topic>Neurons - metabolism</topic><topic>Neuroprotection</topic><topic>Neuroprotective Agents - pharmacology</topic><topic>Receptors, AMPA - antagonists & inhibitors</topic><topic>Receptors, Glycine - antagonists & inhibitors</topic><topic>Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors</topic><topic>Vascular diseases and vascular malformations of the nervous system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hicks, Caroline A.</creatorcontrib><creatorcontrib>Ward, Mark A.</creatorcontrib><creatorcontrib>Ragumoorthy, Nella</creatorcontrib><creatorcontrib>Ambler, Samantha J.</creatorcontrib><creatorcontrib>Dell, Colin P.</creatorcontrib><creatorcontrib>Dobson, David</creatorcontrib><creatorcontrib>O'Neill, Michael J.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Brain research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hicks, Caroline A.</au><au>Ward, Mark A.</au><au>Ragumoorthy, Nella</au><au>Ambler, Samantha J.</au><au>Dell, Colin P.</au><au>Dobson, David</au><au>O'Neill, Michael J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evaluation of glycine site antagonists of the NMDA receptor in global cerebral ischaemia</atitle><jtitle>Brain research</jtitle><addtitle>Brain Res</addtitle><date>1999-02-20</date><risdate>1999</risdate><volume>819</volume><issue>1</issue><spage>65</spage><epage>74</epage><pages>65-74</pages><issn>0006-8993</issn><eissn>1872-6240</eissn><coden>BRREAP</coden><abstract>In the present studies we have investigated the effects of a range of glycine site antagonists of the
N-methyl-
d-aspartate (NMDA) receptor in the gerbil model of global cerebral ischaemia. The compounds tested were (+)-3-amino-1-hydroxy-2-pyrrolidone (HA 966, 15 mg/kg), 7-chloro-4-hydroxy-3-(3-phenoxy)phenyl-2(
H)-quinolinone) (L-701,324, 40 mg/kg), 7-chloro-3-(cyclopropylcarbonyl)-4-hydroxy-2(1
H)-quinolinone) (L-701,252, 50 mg/kg), (3-(3-hydroxyphenyl)prop-2-ynyl 7-chloro-4 hydroxy-2(1
H)-quinolone-3-carboxylate) (L-701,273, 50 mg/kg), 5-nitro-6,7-dichloro-2,3-quinoxalinedione (ACEA 1021, 25 mg/kg) and [(
E)-3[(phenylcarbamoyl) ethenyl]-4,6-dichloroindole-2-carboxylic acid sodium salt (GV 150526A, 40 mg/kg). All compounds were administered via the i.p. route 30 min before and again at 2 h 30 min after 5 min bilateral carotid artery occlusion (BCAO) in the gerbil. For comparison we also evaluated a non-competitive NMDA antagonist, (5
R,10
S)-(+)-5-methyl-10,11-dihydro-5
H-dibenzo[
a,
d]cyclohepten-5,10-imine (MK-801, 2 mg/kg) and an α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) antagonist, (3
S,4a
R, 6
R, 8a
R)-6-[2-(1(2)
H-tetrazole-5-yl)]decahydroisoquinoline-3-carboxylic acid (LY293558, 20 mg/kg). In the present studies L-701,252, L-701,324 and L-701,273 provided a small degree of neuroprotection. ACEA 1021, GV 150526A and HA 966 failed to provide any neuroprotection, while MK-801 provided significant (20%) protection. In contrast LY293558 provided good (55%) neuroprotection. These results indicate that glycine site antagonists and competitive NMDA antagonists provide a small degree of neuroprotection in global cerebral ischaemia. In contrast, AMPA receptor antagonists provide more robust neuroprotection in global cerebral ischaemia.</abstract><cop>London</cop><cop>Amsterdam</cop><cop>New York, NY</cop><pub>Elsevier B.V</pub><pmid>10082862</pmid><doi>10.1016/S0006-8993(98)01329-8</doi><tpages>10</tpages></addata></record> |
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| ispartof | Brain research, 1999-02, Vol.819 (1), p.65-74 |
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| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | ACEA1021 Animals Arterial Occlusive Diseases - complications Biological and medical sciences Carotid Artery Diseases - complications Cell Death - drug effects Cerebral ischaemia Excitatory Amino Acid Antagonists - pharmacology Gerbil Gerbillinae Glycine site antagonist GV150526A Hippocampus - drug effects Hippocampus - metabolism Ischemic Attack, Transient - drug therapy Ischemic Attack, Transient - etiology Ischemic Attack, Transient - pathology L-701 LY293558 Male Medical sciences Neurology Neurons - drug effects Neurons - metabolism Neuroprotection Neuroprotective Agents - pharmacology Receptors, AMPA - antagonists & inhibitors Receptors, Glycine - antagonists & inhibitors Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors Vascular diseases and vascular malformations of the nervous system |
| title | Evaluation of glycine site antagonists of the NMDA receptor in global cerebral ischaemia |
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