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Science 27 April 1984:
Vol. 224. no. 4647, pp. 405 - 407
DOI: 10.1126/science.6608790
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Articles

Science, Vol 224, Issue 4647, 405-407
Copyright © 1984 by American Association for the Advancement of Science

articles

Inhibition of dihydropteridine reductase by novel 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine analogs

CW Abell, RS Shen, W Gessner, and A Brossi

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.




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Science. ISSN 0036-8075 (print), 1095-9203 (online)