Inhibiteurs spécifiques de la recapture de la sérotonine (ISRS) de deuxième génération

Profil de liaison du transporteur de l'escitalopram et de la R-fluoxétine chez l'homme

Translated title of the contribution: Second generation SSRIS: Human monoamine transporter binding profile of escitalopram and R-fluoxetine

J. M. Owens, D. L. Knight, Charles Nemeroff

Research output: Contribution to journalArticle

18 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 serotonine reuptake ihibitors 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 languageFrench
Pages (from-to)350-355
Number of pages6
JournalEncephale
Volume28
Issue number4
StatePublished - Oct 10 2002
Externally publishedYes

Fingerprint

Citalopram
Fluoxetine
Serotonin Plasma Membrane Transport Proteins
Norepinephrine Plasma Membrane Transport Proteins
Affinity
Dopamine Plasma Membrane Transport Proteins
Serotonin Uptake Inhibitors
Dopamine
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

  • Psychiatry and Mental health
  • Neuroscience(all)

Cite this

@article{b28292163c4d4f278ff9b0a4f2017c87,
title = "Inhibiteurs sp{\'e}cifiques de la recapture de la s{\'e}rotonine (ISRS) de deuxi{\`e}me g{\'e}n{\'e}ration: Profil de liaison du transporteur de l'escitalopram et de la R-fluox{\'e}tine chez l'homme",
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 serotonine reuptake ihibitors 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.",
keywords = "Antidepressant, Binding, Enantiomer, Escitalopram R-fluoxetine, S-citalopram, Serotonin, Uptake",
author = "Owens, {J. M.} and Knight, {D. L.} and Charles Nemeroff",
year = "2002",
month = "10",
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language = "French",
volume = "28",
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journal = "L'Encephale",
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T2 - Profil de liaison du transporteur de l'escitalopram et de la R-fluoxétine chez l'homme

AU - Owens, J. M.

AU - Knight, D. L.

AU - Nemeroff, Charles

PY - 2002/10/10

Y1 - 2002/10/10

N2 - 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 serotonine reuptake ihibitors 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.

AB - 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 serotonine reuptake ihibitors 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.

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