ArticleThe Journal of biological chemistry2012
Interaction of antidepressants with the serotonin and norepinephrine transporters: mutational studies of the S1 substrate binding pocket.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 87 citations in OpenAlex.
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- Careful Examination of a Novel Azobenzene Paroxetine Derivative and Its Interactions With Biogenic Amine Transporters.Journal of neurochemistry · 2025Article
- Pharmacological Mechanisms of SLC6 Neurotransmitter Transporter Inhibition.Advances in neurobiology · 2025Review
- Mechanistic insights of substrate transport and inhibitor binding revealed by high-resolution structures of human norepinephrine transporter.Cell research · 2024Article
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- The serotonin transporter sustains human brown adipose tissue thermogenesis.Nature metabolism · 2023Article
- Discovery and Development of Monoamine Transporter Ligands.Advances in neurobiology · 2023Review
- The substrate import mechanism of the human serotonin transporter.Biophysical journal · 2022Article
- Design, Synthesis, and Functional Evaluation of 1, 5-Disubstituted Tetrazoles as Monoamine Neurotransmitter Reuptake Inhibitors.Biomolecules & therapeutics · 2022Article
- Toward Reducing hERG Affinities for DAT Inhibitors with a Combined Machine Learning and Molecular Modeling Approach.Journal of chemical information and modeling · 2021Article
- The antidepressant drug vilazodone is an allosteric inhibitor of the serotonin transporter.Nature communications · 2021Article
- Label-free high-throughput screening assay for the identification of norepinephrine transporter (NET/SLC6A2) inhibitors.Scientific reports · 2021Article
- Structural basis of norepinephrine recognition and transport inhibition in neurotransmitter transporters.Nature communications · 2021Article
- Paroxetine-Overview of the Molecular Mechanisms of Action.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The serotonin transporter (SERT) and the norepinephrine transporter (NET) are sodium-dependent neurotransmitter transporters responsible for reuptake of released serotonin and norepinephrine, respectively, into nerve terminals in the brain. A wide range of inhibitors of SERT and NET are used as treatment of depression and anxiety disorders or as psychostimulant drugs of abuse. Despite their clinical importance, the molecular mechanisms by which various types of antidepressant drugs bind and inhibit SERT and NET are still elusive for the majority of the inhibitors, including the molecular basis for SERT/NET selectivity. Mutational analyses have suggested that a central substrate binding site (denoted the S1 pocket) also harbors an inhibitor binding site. In this study, we determine the effect of mutating six key S1 residues in human SERT (hSERT) and NET (hNET) on the potency of 15 prototypical SERT/NET inhibitors belonging to different drug classes. Analysis of the resulting drug sensitivity profiles provides novel information on drug binding modes in hSERT and hNET and identifies specific S1 residues as important molecular determinants for inhibitor potency and hSERT/hNET selectivity.
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