Document Detail


The toxic actions of MPTP and its metabolite MPP+ are not mimicked by analogues of MPTP lacking an N-methyl moiety.
MedLine Citation:
PMID:  2417166     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), its metabolite 1-methyl-4-phenylpyridine (MPP+) and three analogues of MPTP, lacking an N-methyl moiety, namely, 4-phenylpiperidine (I), 4-phenyl-1,2,3,6-tetrahydropyridine (II) and 4-phenylpyridine (III), were infused continuously for a period of 4 days into the rat substantia nigra. Within 12 h of commencing the bilateral infusion of MPTP or MPP+, rats showed marked motor deficits with reduction in locomotor activity, loss of ability to move the forelimbs and grip with forepaws and, following MPP+ infusions, similar loss of movement in the hindlimbs associated with the development of limb and body rigidity. These motor deficits were not induced by the 3 analogues of MPTP on infusion into the substantia nigra. After 4 days of infusion, the motor deficits caused by MPTP and, in particular, MPP+, were still marked, and for MPP+ these correlated with marked loss of striatal dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid. 4-Phenyl-1,2,3,6-tetrahydropyridine caused a small loss in striatal DA and DOPAC, but the other analogues failed to modify the striatal content of DA or its metabolites. Small alterations of chemical structures related to MPTP and its metabolite can critically alter ability to induce behavioural and neurochemical changes reflecting toxicity on the nigrostriatal DA system.
Authors:
A J Bradbury; B Costall; A M Domeney; B Testa; P G Jenner; C D Marsden; R J Naylor
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Neuroscience letters     Volume:  61     ISSN:  0304-3940     ISO Abbreviation:  Neurosci. Lett.     Publication Date:  1985 Oct 
Date Detail:
Created Date:  1986-02-18     Completed Date:  1986-02-18     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  7600130     Medline TA:  Neurosci Lett     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  121-6     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
1-Methyl-4-phenylpyridinium
3,4-Dihydroxyphenylacetic Acid / analysis
Animals
Brain Diseases / chemically induced
Chemical Phenomena
Chemistry
Corpus Striatum*
Dopamine / analysis
Homovanillic Acid / analysis
Hydroxyindoleacetic Acid / analysis
Male
Movement Disorders / chemically induced*
Norepinephrine / analysis
Pyridines / toxicity*
Pyridinium Compounds / toxicity*
Rats
Serotonin / analysis
Substantia Nigra*
Chemical
Reg. No./Substance:
0/Pyridines; 0/Pyridinium Compounds; 102-32-9/3,4-Dihydroxyphenylacetic Acid; 28289-54-5/1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; 306-08-1/Homovanillic Acid; 48134-75-4/1-Methyl-4-phenylpyridinium; 50-67-9/Serotonin; 51-41-2/Norepinephrine; 54-16-0/Hydroxyindoleacetic Acid

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


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