Document Detail

Extended therapeutic time window after focal cerebral ischemia by non-competitive inhibition of AMPA receptors.
MedLine Citation:
PMID:  16580649     Owner:  NLM     Status:  MEDLINE    
In acute stroke, the therapeutic time window is a critical factor which may have contributed to the failure of several phase III clinical trials with so-called neuroprotective agents. Since cerebral glutamate levels are elevated for many hours in progressing stroke, we investigated the novel AMPA glutamate receptor antagonist ZK 187638 in rodent models of stroke using up to 12 h delays in the start of therapy after permanent occlusion of the middle cerebral artery (MCA). In rats, ZK 187638 reduced total infarct volume by 43% and 33% when therapy was started immediately or with a delay of 6 h, respectively, but no effect was observed after a 12 h delay. Dose-dependent decreases of total infarct volume (up to 42%) were measured in mice given the first injection of ZK 187638 6 h after permanent MCA occlusion. In conclusion, the AMPA receptor antagonist ZK 187638 has a therapeutic time window of at least 6 h after permanent focal cerebral ischemia in rodents.
Bernd Elger; Martin Gieseler; Oliver Schmuecker; Ingrid Schumann; Astrid Seltz; Andreas Huth
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Publication Detail:
Type:  Comparative Study; Journal Article     Date:  2006-04-03
Journal Detail:
Title:  Brain research     Volume:  1085     ISSN:  0006-8993     ISO Abbreviation:  Brain Res.     Publication Date:  2006 Apr 
Date Detail:
Created Date:  2006-05-22     Completed Date:  2006-08-10     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0045503     Medline TA:  Brain Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  189-94     Citation Subset:  IM    
Schering AG, D-13342 Berlin, Germany.
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MeSH Terms
Benzodiazepines / therapeutic use*
Brain Infarction / etiology,  prevention & control
Dioxoles / therapeutic use*
Disease Models, Animal
Dose-Response Relationship, Drug
Infarction, Middle Cerebral Artery / complications,  drug therapy*,  pathology
Receptors, AMPA / antagonists & inhibitors*
Tetrazolium Salts / diagnostic use
Time Factors
Reg. No./Substance:
0/2,3-dimethyl-6-phenyl-12H-(1,3)dioxolo(4,5-h)imidazo(1,2-c)(2,3)benzodiazepine; 0/Dioxoles; 0/Receptors, AMPA; 0/Tetrazolium Salts; 12794-10-4/Benzodiazepines; 902-00-1/triphenyltetrazolium

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