ArticlePsychopharmacology2014
The interaction of escitalopram and R-citalopram at the human serotonin transporter investigated in the mouse.
Article in Psychopharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- The effect of SSRIs on unconditioned anxiety: a systematic review and meta-analysis of animal studies.Psychopharmacology · 2024Pooled it
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- Pharmaco-Multiomics: A New Frontier in Precision Psychiatry.International journal of molecular sciences · 2025Review
- Different Effects of SSRIs, Bupropion, and Trazodone on Mitochondrial Functions and Monoamine Oxidase Isoform Activity.Antioxidants (Basel, Switzerland) · 2023Article
- Hypothyroidism and Diabetes-Related Dementia: Focused on Neuronal Dysfunction, Insulin Resistance, and Dyslipidemia.International journal of molecular sciences · 2022Review
- Investigating an in silico approach for prioritizing antidepressant drug prescription based on drug-induced expression profiles and predicted gene expression.The pharmacogenomics journal · 2021Article
- Encapsulated Escitalopram and Paroxetine Intranasal Co-Administration:Frontiers in pharmacology · 2021Article
- Insights into the mechanism and pharmacology of neurotransmitter sodium symporters.Current opinion in structural biology · 2019Review
- Citalopram inhibits platelet function independently of SERT-mediated 5-HT transport.Scientific reports · 2018Article
- Overview of Monoamine Transporters.Current protocols in pharmacology · 2017Review
- Pharmacometabolomics informs Pharmacogenomics.Metabolomics : Official journal of the Metabolomic Society · 2016Article
- Structural biology: Antidepressants at work.Nature · 2016Article
- Article
- Structure-activity relationship studies of citalopram derivatives: examining substituents conferring selectivity for the allosteric site in the 5-HT transporter.British journal of pharmacology · 2016Article
- In vivo investigation of escitalopram's allosteric site on the serotonin transporter.Pharmacology, biochemistry, and behavior · 2016Article
- Outside the brain: an inside view on transgenic animal and stem cell-based models to examine neuronal serotonin-dependent regulation of HPA axis-controlled events during development and adult stages.Stem cell investigation · 2016Article
Corrections and comments
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Authors and funding
15 authors at 7 institutions in 3 countries.
Funding
Abstract
rationaleEscitalopram appears to be a superior antidepressant to racemic citalopram. It has been hypothesized that binding of R-citalopram to the serotonin transporter (SERT) antagonizes escitalopram binding to and inhibition of the SERT, there by curtailing the elevation of extracellular 5-hydroxytryptamine (5-HTExt), and hence anti-depressant efficacy. Further, it has been suggested that a putative allosteric binding site is important for binding of escitalopram to the primary, orthosteric, site, and for R-citalopram's inhibition here of.
objectivesPrimary: Investigate at the human (h)SERT, at clinical relevant doses, whether R-citalopram antagonizes escitalopram-induced 5-HTExt elevation. Secondary: Investigate whether abolishing the putative allosteric site affects escitalopram-induced 5-HTExt elevation and/or modulates the effect of R-citalopram.
methodsRecombinant generation of hSERT transgenic mice; in vivo microdialysis; SERT binding; pharmacokinetics; 5-HT sensitive behaviors (tail suspension, marble burying).
resultsWe generated mice expressing either the wild-type human SERT (hSERT(WT)) or hSERT carrying amino acid substitutions (A505V, L506F, I507L, S574T and I575T) collectively abolishing the putative allosteric site (hSERT(ALI/VFL+SI/TT)). One mg/kg escitalopram yielded clinical relevant plasma levels and brain levels consistent with therapeutic SERT occupancy. The hSERT mice showed normal basal 5-HTExt levels. Escitalopram-induced 5-HTExt elevation was not decreased by R-citalopram co-treatment and was unaffected by loss of the allosteric site. The behavioral effects of the clinically relevant escitalopram dose were small and tended to be enhanced by R-citalopram co-administration.
conclusionsWe find no evidence that R-citalopram directly antagonizes escitalopram or that the putative allosteric site is important for hSERT inhibition by escitalopram.
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