ArticleNature communications2020
The mechanism of a high-affinity allosteric inhibitor of the serotonin transporter.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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Who cites it
33 citing papers in PubMed, 48 citations in OpenAlex.
- Gut microbiota-targeted interventions for depression in adolescents and young adults: Mechanisms, evidence strength and clinical strategies-A narrative review.General psychiatry · 2026Review
- Modulation of monoaminergic neurotransmission in substance use disorders: a neuropharmacological perspective focusing on plant-derived metabolites.Frontiers in pharmacology · 2026Review
- Screening of selective serotonin reuptake inhibitors from Cyperus rotundus using immobilized neurotransmitter transporter affinity chromatography for antidepressant discovery.Analytical and bioanalytical chemistry · 2025Article
- Deficiency of Rab26 causes behavioral defects in mice through impaired trafficking of serotonin (5-HT) transporter.iScience · 2025Article
- Revealing the location and dynamics of a concealed binding site in the dopamine transporter.Nature communications · 2025Article
- Repurposing serotonergic drugs for gastric cancer: induction of apoptosis in vitro.Molecular biology reports · 2025Article
- Pharmacological Mechanisms of SLC6 Neurotransmitter Transporter Inhibition.Advances in neurobiology · 2025Review
- Substrate Binding and Conformational Dynamics of the Monoamine Transporters.Advances in neurobiology · 2025Review
- (-)-Syringaresinol Exerts an Antidepressant-like Activity in Mice by Noncompetitive Inhibition of the Serotonin Transporter.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Cryo-EM structure of the dopamine transporter with a novel atypical non-competitive inhibitor bound to the orthosteric site.Journal of neurochemistry · 2024Article
- Molecular basis of inhibition of the amino acid transporter BNature communications · 2024Article
- Article
- Allosteric modulation of serotonin and dopamine transporters: New insights from computations and experiments.Current research in physiology · 2024Article
- Dynamic extracellular vestibule of human SERT: Unveiling druggable potential with high-affinity allosteric inhibitors.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Targeting SLC transporters: small molecules as modulators and therapeutic opportunities.Trends in biochemical sciences · 2023Review
- Persistent binding at dopamine transporters determines sustained psychostimulant effects.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Discovery and Development of Monoamine Transporter Ligands.Advances in neurobiology · 2023Review
- SSRI antidepressants differentially modulate serotonin reuptake and release in Drosophila.Journal of neurochemistry · 2022Article
- Unravelling the Turn-On Fluorescence Mechanism of a Fluorescein-Based Probe in GABAAngewandte Chemie (Weinheim an der Bergstrasse, Germany) · 2022Article
- Unravelling the Turn-On Fluorescence Mechanism of a Fluorescein-Based Probe in GABAAngewandte Chemie (International ed. in English) · 2022Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
The serotonin transporter (SERT) terminates serotonin signaling by rapid presynaptic reuptake. SERT activity is modulated by antidepressants, e.g., S-citalopram and imipramine, to alleviate symptoms of depression and anxiety. SERT crystal structures reveal two S-citalopram binding pockets in the central binding (S1) site and the extracellular vestibule (S2 site). In this study, our combined in vitro and in silico analysis indicates that the bound S-citalopram or imipramine in S1 is allosterically coupled to the ligand binding to S2 through altering protein conformations. Remarkably, SERT inhibitor Lu AF60097, the first high-affinity S2-ligand reported and characterized here, allosterically couples the ligand binding to S1 through a similar mechanism. The SERT inhibition by Lu AF60097 is demonstrated by the potentiated imipramine binding and increased hippocampal serotonin level in rats. Together, we reveal a S1-S2 coupling mechanism that will facilitate rational design of high-affinity SERT allosteric inhibitors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.