ArticleScientific reports2016
Mechanism of Paroxetine (Paxil) Inhibition of the Serotonin Transporter.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 54 citations in OpenAlex.
- Identification of novel serotonin transporter (SERT) inhibitors via large-scale machine learning-based virtual screening and molecular dynamics simulations.Molecular diversity · 2026Article
- From In Vitro Genotoxicity Assays to Human Biomarkers: Interpreting DNA Damage Signals in Long-Term SSRI Therapy through a Translational Neurotoxicology Lens.Neurotoxicity research · 2026Review
- Structural basis of vilazodone dual binding mode to the serotonin transporter.Nature communications · 2025Article
- Flunarizine as a potential repurposed drug for the serotonin transporter inhibition: an integrated approach for therapeutic development against major depressive disorder.Frontiers in pharmacology · 2025Article
- (-)-Syringaresinol Exerts an Antidepressant-like Activity in Mice by Noncompetitive Inhibition of the Serotonin Transporter.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Microdosing ketamine in Drosophila does not block serotonin reuptake, but causes complex behavioral changes mediated by glutamate and serotonin receptors.Journal of neurochemistry · 2024Article
- 5-HT_FAsTR: a versatile, label-free, high-throughput, fluorescence-based microplate assay to quantify serotonin transport and release.Scientific reports · 2024Article
- SSRI antidepressants differentially modulate serotonin reuptake and release in Drosophila.Journal of neurochemistry · 2022Article
- Molecular characterization of the serotonergic transporter from the cestode Echinococcus granulosus: pharmacology and potential role in the nervous system.Parasitology research · 2022Article
- Impact of Paroxetine, a Strong CYP2D6 Inhibitor, on SPN-812 (Viloxazine Extended-Release) Pharmacokinetics in Healthy Adults.Clinical pharmacology in drug development · 2021Article
- Assessment of Paroxetine Molecular Interactions with Selected Monoamine and γ-Aminobutyric Acid Transporters.International journal of molecular sciences · 2021Article
- Paroxetine-Overview of the Molecular Mechanisms of Action.International journal of molecular sciences · 2021Review
- Chemical and structural investigation of the paroxetine-human serotonin transporter complex.eLife · 2020Article
- Multitarget Approach to Drug Candidates against Alzheimer's Disease Related to AChE, SERT, BACE1 and GSK3β Protein Targets.Molecules (Basel, Switzerland) · 2020Article
- Computation-guided analysis of paroxetine binding to hSERT reveals functionally important structural elements and dynamics.Neuropharmacology · 2019Article
- A Novel Bromine-Containing Paroxetine Analogue Provides Mechanistic Clues for Binding Ambiguity at the Central Primary Binding Site of the Serotonin Transporter.ACS chemical neuroscience · 2019Article
- Insights into the mechanism and pharmacology of neurotransmitter sodium symporters.Current opinion in structural biology · 2019Review
- eToxPred: a machine learning-based approach to estimate the toxicity of drug candidates.BMC pharmacology & toxicology · 2019Article
- Article
- Structural basis for recognition of diverse antidepressants by the human serotonin transporter.Nature structural & molecular biology · 2018Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The serotonin transporter (SERT) is an integral membrane protein that exploits preexisting sodium-, chloride-, and potassium ion gradients to catalyze the thermodynamically unfavorable movement of synaptic serotonin into the presynaptic neuron. SERT has garnered significant clinical attention partly because it is the target of multiple psychoactive agents, including the antidepressant paroxetine (Paxil), the most potent selective serotonin reuptake inhibitor known. However, the binding site and orientation of paroxetine in SERT remain controversial. To provide molecular insight, we constructed SERT homology models based on the Drosophila melanogaster dopamine transporter and docked paroxetine to these models. We tested the predicted binding configurations with a combination of radioligand binding and flux assays on wild-type and mutant SERTs. Our data suggest that the orientation of paroxetine, specifically its fluorophenyl ring, in SERT's substrate binding site directly depends on this pocket's charge distribution, and thereby provide an avenue toward understanding and enhancing high-affinity antidepressant activity.
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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.