title: Cytotoxicity of 1-amino-4-phenyl-1,2,3,6-tetrahydropyridine and 1-amino-4-phenylpyridinium ion, 1-amino analogues of MPTP and MPP+, to clonal pheochromocytoma PC12 cells.
abstract: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces parkinsonism in humans after its oxidation into 1-methyl-4-phenylpyridinium ion (MPP+) by type B monoamine oxidase. The 1-amino analogues of MPTP and MPP+, 1-amino-4-phenyl-1,2,3, 6-tetrahydropyridine (APTP) and 1-amino-4-phenylpyridinium ion (APP+), were synthesized, and their cytotoxicity to clonal pheochromocytoma PC12 cells was examined using a tetrazolium formazan assay. After incubation for 48 and 72 h, both APP+ and APTP were found to be cytotoxic to PC12 cells, whereas with the N-methyl analogues, only MPP+, but not MPTP, was cytotoxic. The cytotoxicity of APTP increased with incubation time and equaled that of MPP+ after 72 h. It was found that APTP was oxidized to APP+ by type A monoamine oxidase in PC12 cells, suggesting that APP+ itself may damage the cells. In addition to APTP and APP+, N-amino analogues of N-methylisoquinolines and related derivatives were also synthesized and examined for their cytotoxicity to PC12 cells.
authors.affiliation: Faculty of Pharmaceutical Sciences, Nagoya City University, Tanabedori, Mizuho-ku, Nagoya 467, Japan. kohda@phar.nagoya-cu.ac.jp
authors.forename: K
authors.initials: K
authors.lastname: Kohda
authors.forename: Y
authors.initials: Y
authors.lastname: Noda
authors.forename: S
authors.initials: S
authors.lastname: Aoyama
authors.forename: M
authors.initials: M
authors.lastname: Umeda
authors.forename: T
authors.initials: T
authors.lastname: Sumino
authors.forename: T
authors.initials: T
authors.lastname: Kaiya
authors.forename: W
authors.initials: W
authors.lastname: Maruyama
authors.forename: M
authors.initials: M
authors.lastname: Naoi
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D002470:Cell Survival; D015259:Dopamine Agents / Q000633:toxicity*; D020267:MPTP Poisoning; D008996:Monoamine Oxidase Inhibitors / Q000633:toxicity; D010084:Oxidation-Reduction; D016716:PC12 Cells; D051381:Rats
chemical_list: D000970:Antineoplastic Agents; D015259:Dopamine Agents; D008996:Monoamine Oxidase Inhibitors; D015655:1-Methyl-4-phenylpyridinium