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

Background: Single isomers of the selective serotonin reuptake inhibitors c italopram (escitalopram, S-citalopram) and fluoxetine (R-fluoxetine) are cu rrently under development for the treatment of depression and other psychia tric disorders. Previous studies conducted in laboratory animals have revea led that the biological effects on serotonin reuptake for citalopram reside in the S enantiomer. In contrast, both enantiomers of fluoxetine contribut e 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 seroto nin, norepinephrine, and dopamine transporters and several select neurotran smitter receptors using radioligand binding assays. Results: Both escitalopram and R-fluoxetine were potent inhibitors of the s erotonin transporter (K-i = 1.1 and 1.4 nmol/L, respectively). Escitalopram was the most serotonin transporter-selective compound tested and was simil ar to 30-fold more potent than R-citalopram. Conclusions: As noted previously, paroxetine and sertraline possess moderat e affinity (< 50 nmol/L) for the human norepinephrine transporter and dopam ine transporter, respectively. R-Fluoxetine, unlike the other selective ser otonin reuptake inhibitors, possesses moderate affinity (K-i = 64 nmol/L) f or the serotonin 2C receptor. Potential clinical correlates of these unique attributes of escitalopram and R-fluoxetine are discussed. Biol Psychiatry 2001;50: 345-350 (C) 2001 Society of Biological Psychiatry.