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

See allHide authors and affiliations

Science  27 Apr 1984:
Vol. 224, Issue 4647, pp. 405-407
DOI: 10.1126/science.6608790


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.