ArticleNature communications2016
KCNQ channel openers reverse depressive symptoms via an active resilience mechanism.
Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.
What it found
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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
101 citing papers in PubMed, 160 citations in OpenAlex.
- Effects of the KCNQ (Kv7) Channel Opener Ezogabine on Resting-State Functional Connectivity of Striatal Brain Reward Regions, Depression, and Anhedonia in Major Depressive Disorder: Results From a Randomized Controlled Trial.Biological psychiatry · 2025Trial
- Effects of KCNQ potassium channel modulation on ventral tegmental area activity and connectivity in individuals with depression and anhedonia.Molecular psychiatry · 2025Trial
- Azetukalner, a Novel KV7 Potassium Channel Opener, in Adults With Major Depressive Disorder: A Randomized Clinical Trial.JAMA network open · 2025Trial
- Impact of the KCNQ2/3 Channel Opener Ezogabine on Reward Circuit Activity and Clinical Symptoms in Depression: Results From a Randomized Controlled Trial.The American journal of psychiatry · 2021Trial
- Effects of the KCNQ channel opener ezogabine on functional connectivity of the ventral striatum and clinical symptoms in patients with major depressive disorder.Molecular psychiatry · 2020Trial
- Depression in neurodegenerative disease: neurobiological mechanisms and emerging treatments.Molecular psychiatry · 2026Review
- Targeting the dopaminergic midbrain with precision 7-Tesla biofeedback training in depression: A proof-of-principle randomized controlled trial.Molecular psychiatry · 2026Article
- Discovery of Novel Bicyclic Pyrazole Amides as Potent Neuronal KACS medicinal chemistry letters · 2026Article
- Towards precision psychiatry: initial foundations and future directions.Nature reviews. Drug discovery · 2026Review
- Temporal multi-omic exploration of the ventral tegmental area in chronic pain and passive coping behaviors.iScience · 2026Article
- GABAergic Neuron Activation in the RMTg-VTA Pathway Modulates Dopaminergic Neuron Excitability and Social Stress Susceptibility in Male Mice.CNS neuroscience & therapeutics · 2026Article
- New Antidepressant Development in the Treatment of Depression.Advances in experimental medicine and biology · 2026Review
- Anhedonia in Depressive Disorder and Schizophrenia: An Overview of Causes, Diagnosis, and Treatment.Medical science monitor : international medical journal of experimental and clinical research · 2025Review
- Article
- VTA network dominance in depression confers distinct psychopathological states through blunted neural tracking of reward prediction errors.Research square · 2025Article
- Design and validation of novel brain-penetrant HCN channel inhibitors to ameliorate social stress-induced susceptible phenotype.Molecular psychiatry · 2025Article
- Untangling the multifaceted VTA responses to stress.Trends in neurosciences · 2025Review
- The neurobiology of motivational anhedonia in patients with depression.Brain imaging and behavior · 2025Article
- Infralimbic Projections to the Substantia Innominata-Ventral Pallidum Constrain Defensive Behavior during Extinction Learning.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Targeted M-Channel Activation in the Left Stellate Ganglion Protects Against Ischemia-Induced Ventricular Arrhythmias in Canines.Journal of the American Heart Association · 2025Article
41 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 1 country.
Funding
Abstract
Less than half of patients suffering from major depressive disorder, a leading cause of disability worldwide, achieve remission with current antidepressants, making it imperative to develop more effective treatment. A new therapeutic direction is emerging from the increased understanding of natural resilience as an active stress-coping process. It is known that potassium (K(+)) channels in the ventral tegmental area (VTA) are an active mediator of resilience. However, no druggable targets have been identified to potentiate active resilience mechanisms. In the chronic social defeat stress model of depression, we report that KCNQ-type K(+) channel openers, including FDA-approved drug retigabine (ezogabine), show antidepressant efficacy. We demonstrate that overexpression of KCNQ channels in the VTA dopaminergic neurons and either local infusion or systemic administration of retigabine normalized neuronal hyperactivity and depressive behaviours. These findings identify KCNQ as a target for conceptually novel antidepressants that function through the potentiation of active resilience mechanisms.
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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.