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The neuroprotective and neuronal rescue effects of (—)-deprenyl

  • Conference paper
MAO — The Mother of all Amine Oxidases

Part of the book series: Journal of Neural Transmission. Supplement ((NEURAL SUPPL,volume 52))

Summary

The pharmacological effects of (—)-deprenyl is multi-fold in its nature (dopamine sparing activity, neuroprotective and neuronal rescue effects), which cannot be explained solely by the irreversible MAO-B inhibitory action of the substance. Deprenyl slightly inhibits the re-uptake of noradrenaline and dopamine, but methylamphetamine, the metabolite of the inhibitor, by one order of magnitude is more potent in this respect, than the parent compound. Neither the metabolite nor (—)-deprenyl acts on the uptake of serotonin. The inhibitor has an intensive first pass metabolism after oral treatment. The in vivo pharmacokinetic studies with (—)-deprenyl, using the double labelled radioisotope technique (1.5mg/kg; orally) in rats revealed that the molar concentration of methylamphetamine can reach the level suitable to induce a significant inhibition of amine uptake. Deprenyl, but especially methylamphetamine pre-treatment can prevent the noradrenaline release induced by the noradrenergic neurotoxin DSP-4. The uptake inhibitory effect of (—)-deprenyl and the metabolites is reversible. After repeated administration of (—)-deprenyl (1.5mg/kg daily, for 8 days) sustained concentration of its metabolites was detected, compared to that of the acute studies. This can at least partly explain why (—)deprenyl should be administered daily to evoke therapeutic effects in Parkinson’s disease. Administration of (-)deprenyl in a low dose, following the toxic insult, can rescue the damaged neurones. The neuronal rescue effect of the drug was studied on M-1 human melanoma cells in tissue culture. The inhibitor reduced the apoptosis of serum-deprived M-1 cells, but the ( + )-isomer failed to exert this effect. The (±)-desmethyl-deprenyl almost lacks the property to inhibit apoptosis. For neuroprotection and neuronal rescue an optimal dose of (—)-deprenyl should be administered, because to reach a well balanced concentration of the metabolites in tissues is critical.

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Author information

Authors and Affiliations

  1. Departments of Pharmacodynamics, Semmelweis University of Medicine, Budapest, Hungary

    K. Magyar & J. Tarczali

  2. Departments of Pathology and Experimental Cancer Research, Semmelweis University of Medicine, Budapest, Hungary

    B. Szende

  3. Departments of Central Isotope Laboratory, Semmelweis University of Medicine, Budapest, Hungary

    J. Lengyel

  4. Chinoin Pharmaceutical Works, Budapest, Hungary

    I. Szatmáry

  5. Department of Pharmacodynamics, Semmelweis University of Medicine, Nagyvárad tér 4., Budapest, 1089, Hungary

    K. Magyar

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  1. K. Magyar
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  2. B. Szende
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  3. J. Lengyel
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  4. J. Tarczali
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  5. I. Szatmáry
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Editor information

Editors and Affiliations

  1. Department of Pharmacology, The Bruce Rappaport Faculty of Medicine, Technion — Israel Institute of Technology, Haifa, Israel

    J. P. M. Finberg  & M. B. H. Youdim  & 

  2. Clinical Neurochemistry, Department of Psychiatry, University of Würzburg, Federal Republic of Germany

    P. Riederer

  3. Biochemistry Department, Trinity College, Dublin, Ireland

    K. F. Tipton

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© 1998 Springer-Verlag Wien

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Magyar, K., Szende, B., Lengyel, J., Tarczali, J., Szatmáry, I. (1998). The neuroprotective and neuronal rescue effects of (—)-deprenyl. In: Finberg, J.P.M., Youdim, M.B.H., Riederer, P., Tipton, K.F. (eds) MAO — The Mother of all Amine Oxidases. Journal of Neural Transmission. Supplement, vol 52. Springer, Vienna. https://doi.org/10.1007/978-3-7091-6499-0_13

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  • DOI: https://doi.org/10.1007/978-3-7091-6499-0_13

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-211-83037-6

  • Online ISBN: 978-3-7091-6499-0

  • eBook Packages: Springer Book Archive

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