Oxidation of N-methyl(R)salsolinol: involvement to neurotoxicity and neuroprotection by endogenous catechol isoquinolines

  • M. Naoi
  • W. Maruyama
  • T. Kasamatsu
  • P. Dostert
Part of the Journal of Neural Transmission. Supplement book series (NEURAL SUPPL, volume 52)


1(R), 2(N)-Dimethyl-6,7-dihydroxy-l,2,3,4-tetrahydroisoquinoline, N-methyl(R)salsolinol, is a potent dopaminergic neurotoxin to induce parkinsonism in rats. The cytotoxicity of N-methyl(R)salsolinol proved to be ascribed to its oxidation into cytotoxic 1,2-dimethyl-6,7dihydroxyisoquinolinium ion with generation of hydroxyl radical. The isoquinolinium ion caused massive necrosis in the striatum, whereas Nmethyl(R)salsolinol depleted selectively dopaminergic neurons in the substantia nigra without necrotic tissue reaction. N-Methyl(R)salsolinol induced DNA damage to human neuroblastoma SH-SY5Y cells, which could be prevented by anti-oxidants and cycloheximide. These results suggest that oxidative stress through oxidation of N-methyl(R)salsolinol induces apoptotic cell death. On the other hand, (R)salsolinol proved to scavenge hydroxyl radical produced by oxidation of dopamine. The neurotoxicity and neuroprotection of catechol isoquinolines may be ascribed to their oxidation and scavenging of radicals.


Salicylic Acid Substantia Nigra Comet Assay Dopamine Neuron Scavenge Hydroxyl Radical 
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Copyright information

© Springer-Verlag Wien 1998

Authors and Affiliations

  • M. Naoi
    • 1
    • 5
  • W. Maruyama
    • 2
  • T. Kasamatsu
    • 3
  • P. Dostert
    • 4
  1. 1.Department of BiosciencesNagoya Institute of TechnologyGokiso-cho, Showa-kuJapan
  2. 2.Department of BiosciencesNagoya Institute of TechnologyNagoyaJapan
  3. 3.Laboratory of Biochemistry and Metabolism, Department of Basic GerontologyNational Institute for Longevity SciencesObuJapan
  4. 4.Faculty of Pharmaceutical SciencesNagoya City UniversityNagoyaJapan
  5. 5.Pharmacia-UpjohnMilanItaly

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