Dopamine-Derived Isoquinolines as Dopaminergic Neurotoxins and Oxidative Stress

  • Wakako Maruyama
  • Daiichiro Nakahara
  • Philippe Dostert
  • Tsutomu Takahashi
  • Makoto Naoi
Part of the Advances in Behavioral Biology book series (ABBI, volume 44)


Oxygen radicals have been proposed as one of the major factors in neural degeneration in the brain (Youdim et al., 1989; Goetz et al., 1990). In Parkinson’s disease (PD) the involvement of oxygen radicals to the cell death of dopamine (DA) neurons has been strongly suggested. The nigrostriatal system should have specific conditions to increase the vulnerability to oxidative stress, such as high turnover of DA and high consumption of oxygen, and elevated levels of iron and copper. Oxidation of DA by monoamine oxidase [monoamine:oxygen oxidoreductase (deaminating), EC, MAO], produces hydrogen peroxide and further free radicals. In addition, autoxidation of DA produces oxygen radicals (Fornstedt et al., 1990). Recent studies on a dopaminergic neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), reveal that oxidation of MPTP into 1-methyl-4-phenylpyridinium ion (MPP+) by type B MAO is essentially required for the selective neurotoxicity. MPP+ inhibits the oxidative phosphorylation at Complex I of the respiratory chain (Mizuno et al., 1987). In addition, MPP+ releases DA into extracellular space and by its autoxidation free radicals are produced in the brain (Chiueh et al., 1992). These results suggest that production of active oxygen species may be directly involved in the cytotoxicity of neurotoxins.


High Performance Liquid Chromatography Salicylic Acid Monoamine Oxidase Hydroxyl Radical Formation Produce Oxygen Radical 
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Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • Wakako Maruyama
    • 1
  • Daiichiro Nakahara
    • 2
  • Philippe Dostert
    • 3
  • Tsutomu Takahashi
    • 4
  • Makoto Naoi
    • 5
  1. 1.Department of NeurologyNagoya University School of MedicineNagoyaJapan
  2. 2.Department of PsychologyNagoya University College of Medical TechnologyNagoyaJapan
  3. 3.Farmitalia Carlo ErbaResearch and DevelopmentMilanItaly
  4. 4.Department of Food and NutritionKonan Women’s CollegeKonanJapan
  5. 5.Department of BiosciencesNagoya Institute of TechnologyNagoyaJapan

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