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

Kalman Magyar, I. Szatmáry, G. Szebeni, J. Lengyel

Research output: Chapter in Book/Report/Conference proceedingChapter

8 Citations (Scopus)

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, AUC 0-6, AUC0-∞) have been calculated. (-)-Deprenyl is well absorbed after oral and parental treatment. The peak concentrations (C max) 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. After oral treatment the plasma concentrations of methamphetamine are higher during the first 6 h than that of (-)-deprenyl, while the opposite was found after parental treatment. The results indicate, that (-)-deprenyl, a potent MAO-B inhibitor, might induce a different spectrum of activity (e.g. antidepressant), when it is administered parenterally (transdermally). The new spectrum can be due to the special pharmacokinetic behaviour of the inhibitor.

Original languageEnglish
Title of host publicationNeuropsychiatric Disorders An Integrative Approach
EditorsManfred Gerlach, Jurgen Deckert, Kay Double, Eleni Koutsilieri
Pages165-173
Number of pages9
Edition72
DOIs
Publication statusPublished - Dec 1 2007

Publication series

NameJournal of Neural Transmission, Supplementa
Number72
ISSN (Print)0303-6995

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Keywords

  • (-)-Deprenyl
  • deprenyl metabolites
  • pharmacokinetics
  • transdermal application

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

Magyar, K., Szatmáry, I., Szebeni, G., & Lengyel, J. (2007). Pharmacokinetic studies of (-)-deprenyl and some of its metabolites in mouse. In M. Gerlach, J. Deckert, K. Double, & E. Koutsilieri (Eds.), Neuropsychiatric Disorders An Integrative Approach (72 ed., pp. 165-173). (Journal of Neural Transmission, Supplementa; No. 72). https://doi.org/10.1007/978-3-211-73574-9-21