ArticleCurrent neuropharmacology2014
Fluoxetine and all other SSRIs are 5-HT2B Agonists - Importance for their Therapeutic Effects.
Article in Current neuropharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- The Association Between Antidepressant Effect of SSRIs and Astrocytes: Conceptual Overview and Meta-analysis of the Literature.Neurochemical research · 2021Pooled it
- Trial
- Serotonin Transporter Blockade Reduces the Psychedelic-Like Effects of 4-Methoxy-ACS chemical neuroscience · 2026Article
- A structural overview of G-protein-coupled receptors in neurological disorders.Acta pharmacologica Sinica · 2026Review
- Article
- The beneficial effect of fluoxetine on behavioral and cognitive changes in chronic experimental Chagas disease unveils the role of serotonin fueling astrocyte infection by Trypanosoma cruzi.PLoS neglected tropical diseases · 2024Article
- Precision Medicine in Antidepressants Treatment.Handbook of experimental pharmacology · 2023Review
- Fluoxetine treatment during the postpartal period may have short-term impacts on murine maternal skeletal physiology.Frontiers in pharmacology · 2023Article
- An effective nano drug delivery and combination therapy for the treatment of Tuberculosis.Scientific reports · 2022Article
- Fluoxetine inhibited the activation of A1 reactive astrocyte in a mouse model of major depressive disorder through astrocytic 5-HTJournal of neuroinflammation · 2022Article
- Update on GPCR-based targets for the development of novel antidepressants.Molecular psychiatry · 2022Review
- SSRIs: Applications in inflammatory lung disease and implications for COVID-19.Neuropsychopharmacology reports · 2021Review
- Interactions between maternal fluoxetine exposure, the maternal gut microbiome and fetal neurodevelopment in mice.Behavioural brain research · 2021Article
- β-arrestin 2 is essential for fluoxetine-mediated promotion of hippocampal neurogenesis in a mouse model of depression.Acta pharmacologica Sinica · 2021Article
- Serotonergic Facilitation of Forelimb Functional Recovery in Rats with Cervical Spinal Cord Injury.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Article
- Modulation of the Serotonergic Receptosome in the Treatment of Anxiety and Depression: A Narrative Review of the Experimental Evidence.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Gene Expression and In Vitro Pharmacogenetic Studies of Dopamine and Serotonin Gene Receptors in Tuberculosis.Tanaffos · 2021Article
- Fluoxetine Potentiates Phagocytosis and Autophagy in Microglia.Frontiers in pharmacology · 2021Article
- Astroglial Serotonin Receptors as the Central Target of Classic Antidepressants.Advances in neurobiology · 2021Article
- Sleep Deprivation Selectively Down-Regulates Astrocytic 5-HTNeuroscience bulletin · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fluoxetine and other serotonin-specific re-uptake inhibitors (SSRIs) are generally thought to owe their therapeutic potency to inhibition of the serotonin transporter (SERT). However, research in our laboratory showed that it affects, with relatively high affinity the 5-HT2B receptor in cultured astrocytes; this finding was confirmed by independent observations showing that fluoxetine loses its ability to elicit SSRI-like responses in behavioral assays in mice in which the 5-HT2B receptor was knocked-out genetically or inhibited pharmacologically. All clinically used SSRIs are approximately equipotent towards 5-HT2B receptors and exert their effect on cultured astrocytes at concentrations similar to those used clinically, a substantial difference from their effect on SERT. We have demonstrated up-regulation and editing of astrocytic genes for ADAR2, the kainate receptor GluK2, cPLA2 and the 5-HT2B receptor itself after chronic treatment of cultures, which do not express SERT and after treatment of mice (expressing SERT) for 2 weeks with fluoxetine, followed by isolation of astrocytic and neuronal cell fractionation. Affected genes were identical in both experimental paradigms. Fluoxetine treatment also altered Ca(2+) homeostatic cascades, in a specific way that differs from that seen after treatment with the anti-bipolar drugs carbamazepine, lithium, or valproic acid. All changes occurred after a lag period similar to what is seen for fluoxetine's clinical effects, and some of the genes were altered in the opposite direction by mild chronic inescapable stress, known to cause anhedonia, a component of major depression. In the anhedonic mice these changes were reversed by treatment with SSRIs.
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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.