Publication Date:
1984-04-27
Description:
Hydroxylated derivatives of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a nigrostriatal neurotoxin in humans and primates, noncompetitively inhibited dihydropteridine reductase from human liver and rat striatal synaptosomes in vitro at micromolar concentrations. In contrast, MPTP and its chloro- and norderivatives did not inhibit this enzyme at lower than millimolar concentrations. Dihydropteridine reductase converts dihydrobiopterin to tetrahydrobiopterin, the required cofactor for the hydroxylation of aromatic amino acids during the synthesis of dopamine and serotonin.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Abell, C W -- Shen, R S -- Gessner, W -- Brossi, A -- HD 14635/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 1984 Apr 27;224(4647):405-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6608790" target="_blank"〉PubMed〈/a〉
Keywords:
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
;
Animals
;
Corpus Striatum/enzymology
;
Dihydropteridine Reductase/*antagonists & inhibitors
;
Humans
;
Hydroxylation
;
Liver/enzymology
;
NAD/metabolism
;
NADH, NADPH Oxidoreductases/*antagonists & inhibitors
;
Pyridines/*pharmacology
;
Rats
;
Structure-Activity Relationship
;
Synaptosomes/enzymology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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