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.
Keywords
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Article info
Publication history
Accepted:
March 8,
2001
Received in revised form:
February 28,
2001
Received:
November 28,
2000
Identification
Copyright
© 2001 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
