Document Detail


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.
MedLine Citation:
PMID:  9815183     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Chemical research in toxicology     Volume:  11     ISSN:  0893-228X     ISO Abbreviation:  Chem. Res. Toxicol.     Publication Date:  1998 Nov 
Date Detail:
Created Date:  1999-01-11     Completed Date:  1999-01-11     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  8807448     Medline TA:  Chem Res Toxicol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1249-53     Citation Subset:  IM    
Affiliation:
Faculty of Pharmaceutical Sciences, Nagoya City University, Tanabedori, Mizuho-ku, Nagoya 467, Japan. kohda@phar.nagoya-cu.ac.jp
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MeSH Terms
Descriptor/Qualifier:
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
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Dopamine Agents; 0/Monoamine Oxidase Inhibitors; 48134-75-4/1-Methyl-4-phenylpyridinium

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