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.
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© 1994 Springer-Verlag
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Sziráki, I. et al. (1994). Amphetamine-metabolites of deprenyl involved in protection against neurotoxicity induced by MPTP and 2′-methyl-MPTP. In: Tipton, K.F., Youdim, M.B.H., Barwell, C.J., Callingham, B.A., Lyles, G.A. (eds) Amine Oxidases: Function and Dysfunction. Journal of Neural Transmission, vol 41. Springer, Vienna. https://doi.org/10.1007/978-3-7091-9324-2_27
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DOI: https://doi.org/10.1007/978-3-7091-9324-2_27
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