ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2014
Evidence for a role of transporter-mediated currents in the depletion of brain serotonin induced by serotonin transporter substrates.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2014. 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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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
24 citing papers in PubMed, 40 citations in OpenAlex.
- A phase I, randomized, open-label, single-dose, 3-period crossover study to evaluate the drug-drug interaction between ZX008 (fenfluramine HCl oral solution) and a regimen of stiripentol, clobazam, and valproate in healthy subjects .International journal of clinical pharmacology and therapeutics · 2019Trial
- Efficacy of stiripentol, fenfluramine, and their combination on clinical outcomes in Dravet syndrome: A preliminary report.Epilepsia open · 2026Article
- TRACT assay-based in vitro characterization of substituted cathinones: inhibition and release at the serotonin transporter.Archives of toxicology · 2026Article
- Next-Generation MDMA Analogue SDMA: Pharmacological and Metabolic Insights.ACS chemical neuroscience · 2025Article
- Prolintane analogs as hybrid monoamine transporter ligands: Structural determinants and species differences.The Journal of biological chemistry · 2025Article
- Article
- Fenfluramine increases survival and reduces markers of neurodegeneration in a mouse model of Dravet syndrome.Epilepsia open · 2024Article
- Seizures Cause Prolonged Impairment of Ventilation, COThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Fenfluramine: a plethora of mechanisms?Frontiers in pharmacology · 2023Review
- A review on the mitochondrial toxicity of "ecstasy" (3,4-methylenedioxymethamphetamine, MDMA).Current research in toxicology · 2022Article
- An Emerging Role for Sigma-1 Receptors in the Treatment of Developmental and Epileptic Encephalopathies.International journal of molecular sciences · 2021Review
- SCN1B-linked early infantile developmental and epileptic encephalopathy.Annals of clinical and translational neurology · 2019Article
- The synthetic cathinones, butylone and pentylone, are stimulants that act as dopamine transporter blockers but 5-HT transporter substrates.Psychopharmacology · 2019Article
- Effects of N-Alkyl-4-Methylamphetamine Optical Isomers on Plasma Membrane Monoamine Transporters and Abuse-Related Behavior.ACS chemical neuroscience · 2018Article
- N-Alkylated Analogs of 4-Methylamphetamine (4-MA) Differentially Affect Monoamine Transporters and Abuse Liability.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2017Article
- Structure-Activity Relationships of Substituted Cathinones, with Transporter Binding, Uptake, and Release.The Journal of pharmacology and experimental therapeutics · 2017Article
- Amphetamine activates calcium channels through dopamine transporter-mediated depolarization.Cell calcium · 2015Article
- Amphetamine action at the cocaine- and antidepressant-sensitive serotonin transporter is modulated by αCaMKII.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- 'Second-generation' mephedrone analogs, 4-MEC and 4-MePPP, differentially affect monoamine transporter function.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2015Article
- Stereochemistry and neuropharmacology of a 'bath salt' cathinone: S-enantiomer of mephedrone reduces cocaine-induced reward and withdrawal in invertebrates.Neuropharmacology · 2015Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Serotonin (5-HT) transporter (SERT) substrates like fenfluramine and 3,4-methylenedioxymethamphetamine cause long-term depletion of brain 5-HT, while certain other substrates do not. The 5-HT deficits produced by SERT substrates are dependent upon transporter proteins, but the exact mechanisms responsible are unclear. Here, we compared the pharmacology of several SERT substrates: fenfluramine, d-fenfluramine, 1-(m-chlorophenyl)piperazine (mCPP) and 1-(m-trifluoromethylphenyl)piperainze (TFMPP), to establish relationships between acute drug mechanisms and the propensity for long-term 5-HT depletions. In vivo microdialysis was carried out in rat nucleus accumbens to examine acute 5-HT release and long-term depletion in the same subjects. In vitro assays were performed to measure efflux of [(3)H]5-HT in rat brain synaptosomes and transporter-mediated ionic currents in SERT-expressing Xenopus oocytes. When administered repeatedly to rats (6 mg/kg, i.p., four doses), all drugs produce large sustained elevations in extracellular 5-HT (>5-fold) with minimal effects on dopamine. Importantly, 2 weeks after dosing, only rats exposed to fenfluramine and d-fenfluramine display depletion of brain 5-HT. All test drugs evoke fluoxetine-sensitive efflux of [(3)H]5-HT from synaptosomes, but d-fenfluramine and its bioactive metabolite d-norfenfluramine induce significantly greater SERT-mediated currents than phenylpiperazines. Our data confirm that drug-induced 5-HT release probably does not mediate 5-HT depletion. However, the magnitude of transporter-mediated inward current may be a critical factor in the cascade of events leading to 5-HT deficits. This hypothesis warrants further study, especially given the growing popularity of designer drugs that target SERT.
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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.