ReviewInternational journal of molecular sciences2021
An Emerging Role for Sigma-1 Receptors in the Treatment of Developmental and Epileptic Encephalopathies.
Review in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
37 citing papers in PubMed, 3 syntheses or guidelines pooled it, 48 citations in OpenAlex.
- A neuroprotective target in the shadows: a scoping review of pharmacological gaps in σ1R agonists for glutamate-induced neurotoxicity.Frontiers in pharmacology · 2026Pooled it
- Optimal dose of fenfluramine in adjuvant treatment of drug-resistant epilepsy: evidence from randomized controlled trials.Frontiers in neurology · 2024Pooled it
- Pooled it
- Long-term safety and effectiveness of fenfluramine in children and adults with Dravet syndrome.Epilepsia · 2025Trial
- Trial
- Fenfluramine for seizures in Dravet syndrome and Lennox-Gastaut syndrome: Mechanisms, clinical evidence, safety, and practical integration.Epilepsy & behavior reports · 2026Review
- Efficacy and safety of fenfluramine in Dravet syndrome: The impact of patient clinical characteristics.Epilepsia open · 2026Article
- Changes in effectiveness and safety in patients with Lennox-Gastaut syndrome transitioning from the fenfluramine randomized controlled trial to open-label extension study.Epilepsia open · 2026Article
- Effects of fenfluramine and sigma-1-dependent pharmacological and genetic modulation in a mouse kindling model.Epilepsia · 2026Article
- Fenfluramine Attenuates Retinal Microglial Activation but Does Not Rescue Structural and Vascular Deficits in a Rat Model of Dravet Syndrome.International journal of molecular sciences · 2026Article
- Fenfluramine in SCN1A-related GEFS+: A multicenter observational study on efficacy, EEG improvement, and tolerability.Epilepsia open · 2026Observational
- Endocrine Disorders of Calcium Signaling in Children: Neuroendocrine Crosstalk and Clinical Implications.Cells · 2026Review
- From Symptomatic Therapies to Disease-Modifying Approaches for Neuronal Sodium Channel Disorders.International journal of molecular sciences · 2025Review
- Vagus nerve stimulation inEpilepsy & behavior reports · 2025Article
- Voltage-Gated Sodium Channel Dysfunction in Epilepsy: Zebrafish Models for Therapeutics.Biomedicines · 2025Review
- Sigma-1 Receptor Activation by Fluvoxamine Ameliorates ER Stress, Synaptic Dysfunction and Behavioral Deficits in a Ketamine Model of Schizophrenia.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Article
- Expert-Agreed Practical Recommendations on the Use of Fenfluramine in Developmental and Epileptic Encephalopathies Based on Clinical Experience and Literature Review.Neurology and therapy · 2025Review
- Sigma 1 Receptor and Its Pivotal Role in Neurological Disorders.ACS pharmacology & translational science · 2025Review
- Antiseizure Medications: Advancements, Challenges, and Prospects in Drug Development.Current neuropharmacology · 2025Review
- Pharmacovigilance study on old drugs repurposed for rare diseases across different indications: the case of fenfluramine.Frontiers in pharmacology · 2025Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Developmental and epileptic encephalopathies (DEEs) are complex conditions characterized primarily by seizures associated with neurodevelopmental and motor deficits. Recent evidence supports sigma-1 receptor modulation in both neuroprotection and antiseizure activity, suggesting that sigma-1 receptors may play a role in the pathogenesis of DEEs, and that targeting this receptor has the potential to positively impact both seizures and non-seizure outcomes in these disorders. Recent studies have demonstrated that the antiseizure medication fenfluramine, a serotonin-releasing drug that also acts as a positive modulator of sigma-1 receptors, reduces seizures and improves everyday executive functions (behavior, emotions, cognition) in patients with Dravet syndrome and Lennox-Gastaut syndrome. Here, we review the evidence for sigma-1 activity in reducing seizure frequency and promoting neuroprotection in the context of DEE pathophysiology and clinical presentation, using fenfluramine as a case example. Challenges and opportunities for future research include developing appropriate models for evaluating sigma-1 receptors in these syndromic epileptic conditions with multisystem involvement and complex clinical presentation.
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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.