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: K Kohda, Y Noda, S Aoyama, M Umeda, T Sumino, T Kaiya, W Maruyama, M Naoi
• Journal: Chemical research in toxicology (Chem Res Toxicol) Vol. 11 Issue 11 Pg. 1249-53 (Nov 1998) ISSN: 0893-228X [Print] United States
• PMID: 9815183 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Dopamine Agents
• Monoamine Oxidase Inhibitors
• 1-Methyl-4-phenylpyridinium

Topics

• 1-Methyl-4-phenylpyridinium (toxicity)
• Animals
• Antineoplastic Agents (toxicity)
• Cell Survival
• Dopamine Agents (toxicity)
• MPTP Poisoning
• Monoamine Oxidase Inhibitors (toxicity)
• Oxidation-Reduction
• PC12 Cells
• Rats