Document Detail


Ischemic brain damage: reduction by sodium-calcium ion channel modulator RS-87476.
MedLine Citation:
PMID:  2006281     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A novel sodium-calcium ion channel modulator, RS-87476, reduced cerebral infarct size in cats subjected to permanent unilateral occlusion of the middle cerebral artery. Cerebral injury was assessed in vivo with a combination of magnetic resonance (MR) imaging and spectroscopy for 5-12 hours after occlusion and was compared with the area of histochemically ischemic brain tissue. Compared with infarcts in placebo-treated animals, infarcts in cats given RS-87476 were reduced by an average of 70% at the lowest dose, 75% at the intermediate dose, and 88% at the highest dose. Tissue edema, observed as areas of signal hyperintensity on diffusion- and T2-weighted spin-echo images, was confined to small regions of the parietal cortex and basal ganglia in drug-treated animals. Mean plasma levels of RS-87476 at the lowest dose were 13 ng/mL initially, falling to maintenance levels of 3-5 ng/mL; at the intermediate and highest doses, plasma levels of drug were approximately five- and 20-fold greater. The drug was only slightly hypotensive. At least part of the potent cerebroprotective effects of RS-87476 result from its ability to stabilize metabolic energy reserves, reduce lactate formation in ischemic tissues, and attenuate intracerebral edema.
Authors:
J Kucharczyk; J Mintorovitch; M E Moseley; H S Asgari; R J Sevick; N Derugin; D Norman
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Radiology     Volume:  179     ISSN:  0033-8419     ISO Abbreviation:  Radiology     Publication Date:  1991 Apr 
Date Detail:
Created Date:  1991-04-23     Completed Date:  1991-04-23     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0401260     Medline TA:  Radiology     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  221-7     Citation Subset:  AIM; IM    
Affiliation:
Department of Radiology, University of California, San Francisco, School of Medicine 94143.
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MeSH Terms
Descriptor/Qualifier:
Animals
Brain / metabolism,  pathology*
Brain Ischemia / complications,  drug therapy*,  metabolism,  pathology
Cats
Cerebral Infarction / etiology,  pathology
Female
Imidazoles / administration & dosage,  pharmacokinetics,  therapeutic use*
Magnetic Resonance Imaging
Magnetic Resonance Spectroscopy
Male
Piperazines / administration & dosage,  pharmacokinetics,  therapeutic use*
Chemical
Reg. No./Substance:
0/Imidazoles; 0/Piperazines; 119514-66-8/lyfarizine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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