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Amphetamine-metabolites of deprenyl involved in protection against neurotoxicity induced by MPTP and 2′-methyl-MPTP

  • I. Sziráki
  • V. Kardos
  • M. Patthy
  • M. Pátfalusi
  • J. Gaál
  • M. Solti
  • E. Kollár
  • J. Singer
Part of the Journal of Neural Transmission book series (NEURAL SUPPL, volume 41)

Summary

The ability of 1-deprenyl to protect against the parkinsonian effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been attributed to the inhibition of conversion of MPTP to MPP+ (1-methyl-4-phenylpyridinium) catalyzed by MAO-B. We report here that deprenyl-treatment in mice has an additional neuroprotective element associated with the rapid metabolization of 1-deprenyl to 1-methamphetamine and 1-amphetamine. 1-Methamphetamine and 1-amphetamine inhibit MPP+-uptake into striatal synaptosomes prepared from rats. Post-treatment by 1-deprenyl, 1-methamphetamine, 1-amphetamine (at times when MPTP is no longer present in the striatum of mice) protects against neurotoxicity in C57BL mice by blocking the uptake of MPP+ into dopaminergic neurons, and even against the neurotoxicity induced by 2’CH3-MPTP, which is partly bioactivated by MAO-A. These findings may have clinical implications since deprenyl has recently been found to delay the progression of Parkinson’s disease.

Keywords

Dopaminergic Neuron Monoamine Oxidase MPTP Treatment Parkinson Study Group Striatal Level 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • I. Sziráki
    • 1
  • V. Kardos
    • 1
  • M. Patthy
    • 1
  • M. Pátfalusi
    • 1
  • J. Gaál
    • 2
  • M. Solti
    • 2
  • E. Kollár
    • 1
  • J. Singer
    • 1
  1. 1.Institute for Drug ResearchDepartment of Biochemistry IIBudapestHungary
  2. 2.Chinoin Pharmaceutical and Chemical WorksBudapestHungary

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