Source:http://linkedlifedata.com/resource/pubmed/id/15306255
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rdf:type | |
lifeskim:mentions |
umls-concept:C0007785,
umls-concept:C0022116,
umls-concept:C0034693,
umls-concept:C0051318,
umls-concept:C0205234,
umls-concept:C0205355,
umls-concept:C0205374,
umls-concept:C0243076,
umls-concept:C0301630,
umls-concept:C0456389,
umls-concept:C0681850,
umls-concept:C1550501,
umls-concept:C1706203,
umls-concept:C2349001,
umls-concept:C2697811
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pubmed:issue |
1-2
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pubmed:dateCreated |
2004-8-12
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pubmed:abstractText |
Antagonists of 2-amino-3(3-hydroxy-5-methyl-4-isoxazolyl) propionic acid (AMPA) receptors can considerably reduce brain damage after cerebral ischemia, but effectiveness of selective AMPA antagonists has been questioned recently. Therefore, we evaluated the antiischemic efficacy of [+/-]-7-acetyl-5-[4-aminophenyl]-7,8-dihydro-8-cyano-8-methyl-9H-1,3-dioxolo-[4,5-h]-2,3-benzodiazepine (EGIS-8332) and GYKI 53405, two selective, non-competitive AMPA antagonists in two rat models of focal cerebral ischemia. Permanent focal ischemia was produced by electrocoagulation of the middle cerebral artery (MCA). EGIS-8332 and GYKI 53405 were administered 30 min after MCA occlusion at doses of 1, 3 or 10 mg/kg i.p. In transient focal ischemia, MCA was occluded for 1 h and reperfused for 24 h using the intraluminal filament technique and the compounds were given at 3x10 mg/kg i.p. 60, 120 and 180 min following occlusion. In permanent focal ischemia, EGIS-8332 decreased the volume of cerebral infarction both at 10 mg/kg i.p. (36.4%, p<0.01) and at 3 mg/kg i.p. (26.4%, p<0.05) in a dose-dependent manner. GYKI 53405 produced a similar antiischemic effect at 10 mg/kg i.p. (36.4%, p<0.01), but it was ineffective at 3 mg/kg i.p. (6.5%, p=0.57). In transient focal ischemia, EGIS-8332 reduced the volume of necrotic brain tissue (38.7%, p<0.01) and GYKI 53405 was similarly effective (32.6%, p<0.05). Both compounds afforded neuroprotection in the cortical and subcortical regions of the MCA territory. Selective, non-competitive AMPA antagonists administered after the ischemic insult can produce effective neuroprotective action in experimental models of focal cerebral ischemia; therefore, these compounds may be useful as therapeutic agents for the treatment of stroke and neurodegenerative disorders.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0006-8993
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
3
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pubmed:volume |
1019
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
210-6
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:15306255-Animals,
pubmed-meshheading:15306255-Brain Ischemia,
pubmed-meshheading:15306255-Cerebral Infarction,
pubmed-meshheading:15306255-Excitatory Amino Acid Antagonists,
pubmed-meshheading:15306255-Male,
pubmed-meshheading:15306255-Rats,
pubmed-meshheading:15306255-Rats, Sprague-Dawley,
pubmed-meshheading:15306255-Receptors, AMPA
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pubmed:year |
2004
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pubmed:articleTitle |
Reduction of cerebral infarct size by non-competitive AMPA antagonists in rats subjected to permanent and transient focal ischemia.
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pubmed:affiliation |
Pharmacology Laboratory I, Division of Preclinical Research, EGIS Pharmaceuticals Ltd., 1475 Budapest 10 P.O.B. 100, Budapest, Hungary.
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pubmed:publicationType |
Journal Article,
Comparative Study
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