Document Detail


Neuroprotective effect of riluzole in MPTP-treated mice.
MedLine Citation:
PMID:  11684056     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The neuroprotective effects of riluzole, a Na(+) channel blocker with antiglutamatergic activity, and MK-801, a blocker of N-methyl-D-aspartate (NMDA) receptors, were compared in the model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced depletion of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels in mice. The mice were injected intraperitoneally (i.p.) with four administrations of MPTP (10 mg/kg) at 1 h intervals and then the brains were analyzed 1, 3 and 7 days after the treatment. Dopamine and DOPAC levels were significantly decreased in the striatum from 1 day after MPTP treatment. A severe depletion in dopamine and DOPAC levels was found in the striatum 3 and 7 days after MPTP treatment. Riluzole antagonized the MPTP-induced decrease in dopamine, DOPAC and HVA levels in the striatum. On the other hand, MK-801 prevented the MPTP-induced decrease in DOPAC levels, but not in dopamine levels in the striatum. An immunohistochemical study indicated that riluzole can protect against MPTP-induced neuronal damage in the substantia nigra. These results suggest that riluzole is effective against MPTP-induced neurodegeneration of the nigrostriatal dopaminergic neuronal pathway.
Authors:
T Araki; T Kumagai; K Tanaka; M Matsubara; H Kato; Y Itoyama; Y Imai
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Brain research     Volume:  918     ISSN:  0006-8993     ISO Abbreviation:  Brain Res.     Publication Date:  2001 Nov 
Date Detail:
Created Date:  2001-10-30     Completed Date:  2002-01-04     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0045503     Medline TA:  Brain Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  176-81     Citation Subset:  IM    
Affiliation:
Department of Clinical Pharmacology and Therapeutics, Tohoku University Graduate School of Pharmaceutical Science and Medicine, Aoba-yama, Sendai 980-8578, Japan. tsuaraki@mail.cc.tohoku.ac.jp
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MeSH Terms
Descriptor/Qualifier:
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / antagonists & inhibitors*
3,4-Dihydroxyphenylacetic Acid / metabolism
Animals
Dizocilpine Maleate / pharmacology
Dopamine / metabolism*
Dose-Response Relationship, Drug
Drug Interactions / physiology
Excitatory Amino Acid Antagonists / pharmacology*
Glutamic Acid / metabolism
Homovanillic Acid / metabolism
Immunohistochemistry
Male
Mice
Mice, Inbred C57BL
Neostriatum / drug effects*,  metabolism,  physiopathology
Neurons / drug effects,  metabolism
Neuroprotective Agents / pharmacology*
Parkinsonian Disorders / drug therapy*,  metabolism,  physiopathology
Riluzole / pharmacology*
Substantia Nigra / drug effects,  metabolism,  physiopathology
Synaptic Transmission / drug effects,  physiology
Tyrosine 3-Monooxygenase / metabolism
Chemical
Reg. No./Substance:
0/Excitatory Amino Acid Antagonists; 0/Neuroprotective Agents; 102-32-9/3,4-Dihydroxyphenylacetic Acid; 1744-22-5/Riluzole; 28289-54-5/1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; 306-08-1/Homovanillic Acid; 56-86-0/Glutamic Acid; 77086-22-7/Dizocilpine Maleate; EC 1.14.16.2/Tyrosine 3-Monooxygenase

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


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