ArticleMolecular psychiatry2003
Antidepressants are functional antagonists at the serotonin type 3 (5-HT3) receptor.
Article in Molecular psychiatry, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 121 citations in OpenAlex.
- Selective 5HT3 antagonists and sensory processing: a systematic review.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Pooled it
- Boldine Mitigates Chronic Unpredictable Stress-Induced Depression by Suppressing Serotonin 3A Receptor-Calcium/Calmodulin-Dependent Protein Kinase II Signaling and Nucleotide-Binding Domain Leucine-Rich Repeat Protein 3 Inflammasome in the Hippocampus.ACS pharmacology & translational science · 2026Article
- Antidepressant-Like Activity of Naringenin, an Important Agro-Industrial Resource, Complexed with β‑Cyclodextrin.ACS omega · 2026Article
- Molecular Mechanisms of Nicergoline from Ergot Fungus in Blocking Human 5-HT3A Receptor.Journal of microbiology and biotechnology · 2024Article
- Phytoconstituents Targeting the Serotonin 5-HTACS pharmacology & translational science · 2024Review
- 5-HT Receptors and the Development of New Antidepressants.International journal of molecular sciences · 2021Review
- A novel mouse model of glucagon-like peptide-1 receptor expression: A look at the brain.The Journal of comparative neurology · 2020Article
- Bupropion Inhibits Serotonin Type 3AB Heteromeric Channels at Clinically Relevant Concentrations.Molecular pharmacology · 2020Article
- Selective serotonin reuptake inhibitor escitalopram inhibits 5-HTThe Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2019Article
- Multi-modal antidepressant-like action of 6- and 7-chloro-2-aminodihydroquinazolines in the mouse tail suspension test.Psychopharmacology · 2019Article
- Tricyclic antidepressant amitriptyline inhibits 5-hydroxytryptamine 3 receptor currents in NCB-20 cells.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2018Article
- Molecular basis of atypicality of bupropion inferred from its receptor engagement in nervous system tissues.Psychopharmacology · 2018Article
- Single Administration of HBK-15-a Triple 5-HTMolecular neurobiology · 2018Article
- Response of Htr3a knockout mice to antidepressant treatment and chronic stress.British journal of pharmacology · 2017Article
- The antidepressant bupropion is a negative allosteric modulator of serotonin type 3A receptors.Neuropharmacology · 2017Article
- Serotonin Receptor 5-HT3A Affects Development of Bladder Innervation and Urinary Bladder Function.Frontiers in neuroscience · 2017Article
- Paroxetine suppresses recombinant human P2X7 responses.Purinergic signalling · 2015Article
- Inhibition of temporomandibular joint input to medullary dorsal horn neurons by 5HT3 receptor antagonist in female rats.Neuroscience · 2015Article
- Antidepressant-like effects of a novel 5-HT3 receptor antagonist 6z in acute and chronic murine models of depression.Acta pharmacologica Sinica · 2014Article
- Fluoxetine blocks Nav1.5 channels via a mechanism similar to that of class 1 antiarrhythmics.Molecular pharmacology · 2014Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Antidepressants are commonly supposed to enhance serotonergic and/or noradrenergic neurotransmission by inhibition of neurotransmitter reuptake through binding to the respective neurotransmitter transporters or through inhibition of the monoamine oxidase. Using the concentration-clamp technique and measurements of intracellular Ca2+, we demonstrate that different classes of antidepressants act as functional antagonists at the human 5-HT3A receptor stably expressed in HEK 293 cells and at endogenous 5-HT3 receptors of rat hippocampal neurons and N1E-115 neuroblastoma cells. The tricyclic antidepressants desipramine, imipramine, and trimipramine, the serotonin reuptake inhibitor fluoxetine, the norepinephrine reuptake inhibitor reboxetine, and the noradrenergic and specific serotonergic antidepressant mirtazapine effectively reduced the serotonin-induced Na(+)- and Ca(2)(+)-currents in a dose-dependent fashion. This effect was voltage-independent and, with the exception of mirtazapine, noncompetitive. Desipramine, imipramine, trimipramine, and fluoxetine also accelerated receptor desensitization. Moclobemide and carbamazepine had no effect on the serotonin-induced cation current. By analyzing analogues of desipramine and carbamazepine, we found that a basic propylamine side chain increases the antagonistic potency of tricyclic compounds, whereas it is abolished by an uncharged carboxamide group. The antagonistic effects of antidepressants at the 5-HT3 receptor did not correlate with their effects on membrane fluidity. In conclusion, structurally different types of antidepressants modulate the function of this ligand-gated ion channel. This may represent a yet unrecognized pharmacological principle of antidepressants.
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