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

Biol Psychiatry. 2001 Sep 1;50(5):345-50. doi: 10.1016/s0006-3223(01)01145-3.

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 (K(i) = 1.1 and 1.4 nmol/L, respectively). Escitalopram was the most serotonin transporter-selective compound tested and was approximately 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 (K(i) = 64 nmol/L) for the serotonin 2C receptor. Potential clinical correlates of these unique attributes of escitalopram and R-fluoxetine are discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding, Competitive
  • Brain / metabolism
  • Carrier Proteins / metabolism*
  • Citalopram / pharmacokinetics*
  • Dopamine Plasma Membrane Transport Proteins
  • Dose-Response Relationship, Drug
  • Fluoxetine / pharmacokinetics*
  • Humans
  • Membrane Glycoproteins / metabolism*
  • Membrane Transport Proteins*
  • Nerve Tissue Proteins*
  • Norepinephrine Plasma Membrane Transport Proteins
  • Receptors, Neurotransmitter / metabolism*
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin Uptake Inhibitors / pharmacokinetics*
  • Stereoisomerism
  • Structure-Activity Relationship
  • Symporters*

Substances

  • Carrier Proteins
  • Dopamine Plasma Membrane Transport Proteins
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Norepinephrine Plasma Membrane Transport Proteins
  • Receptors, Neurotransmitter
  • SLC6A2 protein, human
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin Uptake Inhibitors
  • Symporters
  • Fluoxetine
  • Citalopram