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Pharmacokinetic studies of (—)-deprenyl and some of its metabolites in mouse

  • Conference paper
Neuropsychiatric Disorders An Integrative Approach

Part of the book series: Journal of Neural Transmission. Supplementa ((NEURALTRANS,volume 72))

Abstract

(—)-Deprenyl is a selective irreversible inhibitor of MAO-B. The parent compound is responsible for the enzyme inhibitory effect, but its metabolites are also playing a role in the complex pharmacological activity of the substance. In the present studies male NMRI mice were treated orally, subcutaneously, intraperitoneally and intravenously with 5mg/kg of (—)-deprenyl. The time related changes of the plasma concentrations of the parent compound and its main metabolites (methamphetamine, desmethyl-deprenyl and amphetamine) were determined by GC/ MSD technique. The main pharmacokinetic parameters (Cmax, tmax, t1/2 β, AUC0–6, AUC0-∞) have been calculated. (—)-Deprenyl is well absorbed after oral and parental treatment. The peak concentrations (Cmax) were reached at 15 min after treatment and the absorption was followed by a fast elimination (t1/2 β ≤ 2h). (—)-Deprenyl has an intensive “first pass” metabolism after oral treatment; only 25% of the parent compound reaches the systemic circulation. Increased bioavailability was detected after subcutaneous (87.1%) and intraperitoneal (78.7%) administration. The main metabolic pathway of (—)-deprenyl is the N-depropargylation, leading to the formation of methamphetamine. N-demethylation of (—)-deprenyl leads to formation of desmethyl-deprenyl. Amphetamine is produced from both former metabolites.

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Authors and Affiliations

  1. Department of Pharmacodynamics, Central Isotope Laboratory, Semmelweis University, P.O. Box 370, Budapest, 1445, Hungary

    Dr. K. Magyar

  2. Metabolism and Pharmacokinetics, Chinoin Private Co. Ltd. (Sanofi-Aventis Group), Budapest, Hungary

    I. Szatmáry & G. Szebeni

  3. Central Isotope Laboratory, Semmelweis University, Budapest, Hungary

    Dr. K. Magyar & J. Lengyel

Authors
  1. Dr. K. Magyar
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  2. I. Szatmáry
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  3. G. Szebeni
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  4. J. Lengyel
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Editors and Affiliations

  1. Klinik und Poliklinik für Kinder- und Jugendpsychiatrie und Psychotherapie, Würzburg, Germany

    M. Gerlach

  2. Klinik und Poliklinik für Psychiatrie und Psychotherapie, Würzburg, Germany

    Jürgen Deckert

  3. Prince of Wales Medical Research Institute, Sydney, Australia

    K. Double

  4. Institut für Virologie und Immunobiologie, Würzburg, Germany

    E. Koutsilieri

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© 2007 Springer-Verlag

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Magyar, K., Szatmáry, I., Szebeni, G., Lengyel, J. (2007). Pharmacokinetic studies of (—)-deprenyl and some of its metabolites in mouse. In: Gerlach, M., Deckert, J., Double, K., Koutsilieri, E. (eds) Neuropsychiatric Disorders An Integrative Approach. Journal of Neural Transmission. Supplementa, vol 72. Springer, Vienna. https://doi.org/10.1007/978-3-211-73574-9_21

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  • DOI: https://doi.org/10.1007/978-3-211-73574-9_21

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-211-73573-2

  • Online ISBN: 978-3-211-73574-9

  • eBook Packages: MedicineMedicine (R0)

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