ArticleMolecular psychiatry2004
Antipsychotic drugs antagonize human serotonin type 3 receptor currents in a noncompetitive manner.
Article in Molecular psychiatry, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 2 of them syntheses 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
28 citing papers in PubMed, 2 syntheses or guidelines pooled it, 67 citations in OpenAlex.
- Selective 5HT3 antagonists and sensory processing: a systematic review.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Pooled it
- 5-HTCurrent neuropharmacology · 2021Pooled it
- Mismatch negativity as an index of target engagement for excitation/inhibition-based treatment development: a double-blind, placebo-controlled, randomized, single-dose cross-over study of the serotonin type-3 receptor antagonist CVN058.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Trial
- Role of 5-hydroxytryptamine type 3 receptors in aerobic exercise-induced improvement of memory and hippocampal synaptic plasticity.Neural regeneration research · 2026Article
- Atypical antipsychotic drug olanzapine inhibits 5-HTThe Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2025Article
- Haloperidol, a typical antipsychotic, inhibits 5-HTThe Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2025Article
- Hydroxy Pentacyclic Triterpene Acid, Kaempferol, Inhibits the Human 5-Hydroxytryptamine Type 3A Receptor Activity.International journal of molecular sciences · 2022Article
- Comparison of Efficacy and Safety Between Low-Dose Ziprasidone in Combination With Sertraline and Ziprasidone Monotherapy for Treatment-Resistant Patients With Acute Exacerbation Schizophrenia: A Randomized Controlled Trial.Frontiers in pharmacology · 2022Article
- 5-HT Receptors and the Development of New Antidepressants.International journal of molecular sciences · 2021Review
- Structure, Function and Physiology of 5-Hydroxytryptamine Receptors Subtype 3.Sub-cellular biochemistry · 2021Review
- Bupropion Inhibits Serotonin Type 3AB Heteromeric Channels at Clinically Relevant Concentrations.Molecular pharmacology · 2020Article
- Antidepressant effect of the interaction of fluoxetine with granisetron.Experimental and therapeutic medicine · 2019Article
- Exercise-induced hippocampal neurogenesis: 5-HTMolecular psychiatry · 2018Article
- Clozapine-induced acute gastrointestinal necrosis: a case report.Journal of medical case reports · 2017Article
- Molecular mechanisms of serotonergic action of the HIV-1 antiretroviral efavirenz.Pharmacological research · 2016Article
- Association Study of Serotonin 3 Receptor Subunit Gene Variants in Antipsychotic-Induced Weight Gain.Neuropsychobiology · 2016Article
- The alpha-7 nicotinic receptor partial agonist/5-HT3 antagonist RG3487 enhances cortical and hippocampal dopamine and acetylcholine release.Psychopharmacology · 2014Article
- Allosteric modulation of the 5-HT(3) receptor.Current opinion in pharmacology · 2011Review
- Impact of lipid raft integrity on 5-HT3 receptor function and its modulation by antidepressants.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2010Article
- Identification of a domain which affects kinetics and antagonistic potency of clozapine at 5-HT3 receptors.PloS one · 2009Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The serotonin type 3 (5-HT(3)) receptor is the only ligand-gated ion channel receptor for serotonin (5-HT). 5-HT(3) receptors play an important role in modulating the inhibitory action of dopamine in mesocorticolimbic brain regions. Neuroleptic drugs are commonly thought to exert their psychopharmacological action mainly through dopamine and serotonin type 2 (5-HT(2)) receptors. Except for clozapine, a direct pharmacological interaction of neuroleptics with 5-HT(3) receptors has not yet been described. Using the concentration-clamp technique, we investigated the effects of flupentixol, various phenothiazines, haloperidol, clozapine and risperidone on Na(+)-inward currents through 5-HT(3) receptors stably expressed in human embryonic kidney 293 cells, and through endogenous 5-HT(3) receptors of murine N1E-115 neuroblastoma cells. In addition, we studied their effects on Ca(2+) influx, measured as a change in intracellular Ca(2+) concentrations ([Ca(2+)](i)). All neuroleptic drugs, but not risperidone, antagonized Na(+)- and Ca(2+)-inward currents evoked by 5-HT (10 microM for 2 s and 1 microM, respectively) in a voltage-independent manner. Only clozapine was a competitive antagonist, while all other compounds turned out to be noncompetitive. Fluphenazine and haloperidol affected membrane anisotropy at concentrations below their IC(50) values, indicating that a change in membrane anisotropy might contribute to their antagonistic effect at the 5-HT(3) receptor. Only structure analogues of flupentixol and fluphenazine with a lipophilic side chain were potent antagonists against 5-HT-evoked Na(+) and Ca(2+) currents. Since 5-HT(3) receptors modulate mesolimbic and mesocortical dopaminergic activity, the functional antagonism of neuroleptics at 5-HT(3) receptors may contribute to their antipsychotic efficacy and may constitute a not yet recognized pharmacological principle of these drugs.
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