PET neuroimaging of [11C]mirtazapine enantiomers in pigs

Donald F. Smith, Katalin Marthi, Ole L. Munk, Paul Cumming, Søren B. Hansen, Steen Jakobsen

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Previously, we used positron emission tomography (PET) for studying the pharmacokinetics of rac-[11C]mirtazapine in living brain. Our findings showed that rac-[11C]mirtazapine has suitable properties for PET neuroimaging. However, separate studies of enantiomers are typically required for characterizing the pharmacokinetics of a racemic drug. Therefore, we have determined the whole-body distribution and brain pharmacokinetics of S- and R-[11C]mirtazapine in pigs. The enantiomers of [11C]mirtazapine produced similar effective doses of radioactivity in most body organs, except for the brain, in which the dose was ∼ 40% higher after injection of S-[11C]mirtazapine than the antipode. Kinetic analyses of dynamic brain PET recordings showed that values for regional accumulation of compound (k3) were significantly higher for S-[11C]mirtazapine than for the antipode, while the values for clearance of compounds from tissue to circulation (k2) were consistently lower for S-[11C]mirtazapine than for the R-form. No reliable difference occurred in the rate of metabolism of S- and R-[11C]mirtazapine in the bloodstream of the pigs. The present findings indicate that enantioselective processes affect the cerebral pharmacokinetics of rac-mirtazapine.

Original languageEnglish
Pages (from-to)350-357
Number of pages8
JournalEuropean Neuropsychopharmacology
Volume16
Issue number5
DOIs
Publication statusPublished - Jul 1 2006

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Keywords

  • Antidepressant
  • Enantiomers
  • PET neuroimaging
  • Pharmacokinetics
  • Porcine brain
  • [C]Mirtazapine

ASJC Scopus subject areas

  • Pharmacology
  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry
  • Pharmacology (medical)

Cite this

Smith, D. F., Marthi, K., Munk, O. L., Cumming, P., Hansen, S. B., & Jakobsen, S. (2006). PET neuroimaging of [11C]mirtazapine enantiomers in pigs. European Neuropsychopharmacology, 16(5), 350-357. https://doi.org/10.1016/j.euroneuro.2005.10.008