In vitro formation of selegiline-N-oxide as a metabolite of selegiline in human, hamster, mouse, rat, guinea-pig, rabbit and dog

Ferenc Lévai, Erzsébet Fejér, Gábor Szeleczky, Anna Szabó, Tünde Eros-Takácsy, Félix Hajdu, Gyula Szebeni, István Szatmári, I. Hermecz

Research output: Contribution to journalArticle

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Abstract

It is well established in the litrature, that selegiline is metabolised to its N-dealkylated metabolites, N-desmethylselegiline, methamphetamine and amphetamine. However, most studies on selegiline metabolism did not characterize the species differences in the formation of the metabolites. Therefore, in this study, we investigated the in vitro metabolism of selegiline in liver microsomes of different species. In addition, to the previously well-characterized metabolites, selegiline-N-oxide (selegiline-NO) was found to be formed as a metabolite of selegiline in rat liver microsomal preparation. The results of experiments with liver microsomes from other species indicated species differences in the rate and extent of formation of selegiline-NO. The dog and hamster liver microsomal preparations were the most active in terms of selegiline-NO production, whereas little selegiline was metabolized to its N-oxide in human liver microsomes. When selegiline-NO was incubated with rat liver microsomes, no metabolism occurred. When a short incubation time was applied in selegiline expriments no increase in the amount of selegiline-NO was detected. Accordingly, it was clear that selegiline was not metabolized to the N-dealkylated or N,N-bis-dealkylated compounds via selegiline-NO. Studies with different isoenzyme inhibitors indicated that the formation of selegiline-NO might be catalyzed at least partly by cytochrome P450 (CYP) 2D6 and CYP3A4. With the exception of hamster microsomes in the microsomal preparations in vitro, the formation of the R,S-stereoisomer of selegiline-NO was preferred.

Original languageEnglish
Pages (from-to)169-178
Number of pages10
JournalEuropean Journal of Drug Metabolism and Pharmacokinetics
Volume29
Issue number3
Publication statusPublished - Jul 2004

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Selegiline
Cricetinae
Guinea Pigs
Dogs
Rabbits
Liver Microsomes
Cytochrome P-450 CYP3A
Cytochrome P-450 CYP2D6
Stereoisomerism
Methamphetamine
selegiline-N-oxide
In Vitro Techniques
Liver
Amphetamine
Microsomes
Oxides
Isoenzymes

Keywords

  • CYP2D6
  • CYP3A4
  • Dog
  • Guinea-pig
  • Hamster
  • Human
  • In vitro metabolism
  • Liver microsomes
  • Mouse
  • Rabbit
  • Rat
  • Selegiline
  • Selegiline-N-oxide

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

In vitro formation of selegiline-N-oxide as a metabolite of selegiline in human, hamster, mouse, rat, guinea-pig, rabbit and dog. / Lévai, Ferenc; Fejér, Erzsébet; Szeleczky, Gábor; Szabó, Anna; Eros-Takácsy, Tünde; Hajdu, Félix; Szebeni, Gyula; Szatmári, István; Hermecz, I.

In: European Journal of Drug Metabolism and Pharmacokinetics, Vol. 29, No. 3, 07.2004, p. 169-178.

Research output: Contribution to journalArticle

Lévai, F, Fejér, E, Szeleczky, G, Szabó, A, Eros-Takácsy, T, Hajdu, F, Szebeni, G, Szatmári, I & Hermecz, I 2004, 'In vitro formation of selegiline-N-oxide as a metabolite of selegiline in human, hamster, mouse, rat, guinea-pig, rabbit and dog', European Journal of Drug Metabolism and Pharmacokinetics, vol. 29, no. 3, pp. 169-178.
Lévai, Ferenc ; Fejér, Erzsébet ; Szeleczky, Gábor ; Szabó, Anna ; Eros-Takácsy, Tünde ; Hajdu, Félix ; Szebeni, Gyula ; Szatmári, István ; Hermecz, I. / In vitro formation of selegiline-N-oxide as a metabolite of selegiline in human, hamster, mouse, rat, guinea-pig, rabbit and dog. In: European Journal of Drug Metabolism and Pharmacokinetics. 2004 ; Vol. 29, No. 3. pp. 169-178.
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AU - Lévai, Ferenc

AU - Fejér, Erzsébet

AU - Szeleczky, Gábor

AU - Szabó, Anna

AU - Eros-Takácsy, Tünde

AU - Hajdu, Félix

AU - Szebeni, Gyula

AU - Szatmári, István

AU - Hermecz, I.

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