- 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
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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.
- Kohda, Kohfuku,Noda, Yasuhiro,Aoyama, Shinsuke,Umeda, Michi,Sumino, Tomoe,Kaiya, Toyo,Maruyama, Wakako,Naoi, Makoto
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