PT  - JOURNAL ARTICLE
AU  - K Chiba
AU  - L A Peterson
AU  - K P Castagnoli
AU  - A J Trevor
AU  - N Castagnoli, Jr
TI  - Studies on the molecular mechanism of bioactivation of the selective nigrostriatal toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
DP  - 1985 May 01
TA  - Drug Metabolism and Disposition
PG  - 342--347
VI  - 13
IP  - 3
4099  - http://dmd.aspetjournals.org/content/13/3/342.short
4100  - http://dmd.aspetjournals.org/content/13/3/342.full
SO  - Drug Metab Dispos1985 May 01; 13
AB  - Detailed studies have been carried out on the monoamine oxidase B-catalyzed bioactivation of the nigrostriatal toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) by rat brain mitochondrial preparations. Isolates of incubation mixtures run in H2O and D2O displayed chemical ionization mass spectral characteristics expected for the 1-methyl-4-phenyl-2,3-dihydropyridinium species MPDP+, a proposed intermediate in the biotransformation of MPTP to the 1-methyl-4-phenylpyridinium metabolite (MPP+) previously characterized in both in vitro and in vivo experiments. Further characterization of MPDP+ was achieved by comparison of the diode array UV spectral tracings of the metabolite with synthetic MPDP+ perchlorate (CIO4-) and by the isolation of a cyano adduct from mitochondrial coincubation mixtures of MPTP and sodium cyanide. MPDP+ CIO4- was shown to undergo disproportionation to MPP+ and MPTP, a reaction which suggests that this molecule may participate in redox reactions with dopamine that could lead to neurotoxic oxidation products.