Document Detail


Riluzole protects from motor deficits and striatal degeneration produced by systemic 3-nitropropionic acid intoxication in rats.
MedLine Citation:
PMID:  9300407     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The putative neuroprotective effect of riluzole was investigated in a rat model of progressive striatal neurodegeneration induced by prolonged treatment (three weeks, intraperitoneal) with 3-nitropropionic acid, an irreversible inhibitor of succinate dehydrogenase. Quantitative analysis of motor behaviour indicated a significant protective effect (60%) of riluzole (8 mg/kg/day) on 3-nitropropionic acid-induced motor deficits as assessed using two independent motor tests. Furthermore, quantitative analysis of 3-nitropropionic acid-induced lesions indicated a significant 84% decrease in the volume of striatal damage produced by 3-nitropropionic acid, the neuroprotective effect apparently being more pronounced in the posterior striatum and pallidum. In addition, it was checked that this neuroprotective effect of riluzole against systemic 3-nitropropionic acid did not result from a decreased bioavailability of the neurotoxin or a direct action of riluzole on 3-nitropropionic acid-induced inhibition of succinate dehydrogenase. We found that riluzole significantly decreased by 48% the size of striatal lesions produced by stereotaxic intrastriatal injection of malonate, a reversible succinate dehydrogenase inhibitor. Furthermore, the inhibition of cortical and striatal succinate dehydrogenase activity induced by systemic 3-nitropropionic acid was left unchanged by riluzole administration. The present results, consistent with a beneficial effect of riluzole in amyotrophic lateral sclerosis, suggest that this compound may be useful in the treatment of chronic neurodegenerative diseases.
Authors:
M C Guyot; S Palfi; J M Stutzmann; M Mazière; P Hantraye; E Brouillet
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Neuroscience     Volume:  81     ISSN:  0306-4522     ISO Abbreviation:  Neuroscience     Publication Date:  1997 Nov 
Date Detail:
Created Date:  1997-11-06     Completed Date:  1997-11-06     Revised Date:  2005-11-17    
Medline Journal Info:
Nlm Unique ID:  7605074     Medline TA:  Neuroscience     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  141-9     Citation Subset:  IM    
Affiliation:
Service Hospitalier Frédéric Joliot, Unité de Recherche Associée 2210 Commissariat à l'Energie Atomique-Centre National de la Recherche Scientifique, Département de Recherche Médicale, Orsay, France.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antihypertensive Agents / toxicity*
Corpus Striatum / pathology,  physiopathology*
Injections, Intraperitoneal
Male
Malonates / toxicity
Microinjections
Movement Disorders / drug therapy*,  mortality
Neuroprotective Agents / pharmacology*
Neurotoxins / toxicity
Nitro Compounds
Propionic Acids / toxicity*
Rats
Rats, Sprague-Dawley
Riluzole / pharmacology*
Succinate Dehydrogenase / antagonists & inhibitors
Survival Analysis
Chemical
Reg. No./Substance:
0/Antihypertensive Agents; 0/Malonates; 0/Neuroprotective Agents; 0/Neurotoxins; 0/Nitro Compounds; 0/Propionic Acids; 141-82-2/malonic acid; 1744-22-5/Riluzole; 504-88-1/3-nitropropionic acid; EC 1.3.99.1/Succinate Dehydrogenase

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


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