Second-generation SSRIs: Human monoamine transporter binding profile of escitalopram and R-fluoxetine

Michael J. Owens, David L. Knight, Charles Nemeroff

Research output: Contribution to journalArticle

389 Citations (Scopus)

Abstract

Background: Single isomers of the selective serotonin reuptake inhibitors citalopram (escitalopram, S-citalopram) and fluoxetine (R-fluoxetine) are currently under development for the treatment of depression and other psychiatric disorders. Previous studies conducted in laboratory animals have revealed that the biological effects on serotonin reuptake for citalopram reside in the S enantiomer. In contrast, both enantiomers of fluoxetine contribute to its biological activity. Methods: In the present study, the potency and selectivity of escitalopram, R-fluoxetine, and all of the other currently available selective serotonin reuptake inhibitors were compared for binding affinity at the human serotonin, norepinephrine, and dopamine transporters and several select neurotransmitter receptors using radioligand binding assays. Results: Both escitalopram and R-fluoxetine were potent inhibitors of the serotonin transporter (Ki = 1.1 and 1.4 nmol/L, respectively). Escitalopram was the most serotonin transporter-selective compound tested and was ∼30-fold more potent than R-citalopram. Conclusions: As noted previously, paroxetine and sertraline possess moderate affinity (<50 nmol/L) for the human norepinephrine transporter and dopamine transporter, respectively. R-Fluoxetine, unlike the other selective serotonin reuptake inhibitors, possesses moderate affinity (Ki = 64 nmol/L) for the serotonin 2C receptor. Potential clinical correlates of these unique attributes of escitalopram and R-fluoxetine are discussed.

Original languageEnglish
Pages (from-to)345-350
Number of pages6
JournalBiological Psychiatry
Volume50
Issue number5
DOIs
StatePublished - Sep 1 2001
Externally publishedYes

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Citalopram
Fluoxetine
Serotonin Plasma Membrane Transport Proteins
Serotonin Uptake Inhibitors
Norepinephrine Plasma Membrane Transport Proteins
Dopamine Plasma Membrane Transport Proteins
Receptor, Serotonin, 5-HT2C
Sertraline
Paroxetine
Radioligand Assay
Neurotransmitter Receptor
Laboratory Animals

Keywords

  • Antidepressant
  • Binding
  • Enantiomer
  • Escitalopram
  • R-fluoxetine
  • S-citalopram
  • Serotonin
  • Uptake

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

Second-generation SSRIs : Human monoamine transporter binding profile of escitalopram and R-fluoxetine. / Owens, Michael J.; Knight, David L.; Nemeroff, Charles.

In: Biological Psychiatry, Vol. 50, No. 5, 01.09.2001, p. 345-350.

Research output: Contribution to journalArticle

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