ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2018
Antimanic Efficacy of a Novel Kv3 Potassium Channel Modulator.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- KFrontiers in pharmacology · 2026Pooled it
- Optimization of Pyrazole-Based Activators of Kv3.1.ACS medicinal chemistry letters · 2026Article
- AProceedings of the National Academy of Sciences of the United States of America · 2026Article
- From venom peptides to neurotherapeutics: BmK defensins and short-chain peptides as modulators of ion channels.Frontiers in pharmacology · 2026Review
- Recent advances in the pharmacology of voltage-gated ion channels.Pharmacological reviews · 2025Review
- Structural insights into the function, dysfunction and modulation of Kv3 channels.Neuropharmacology · 2025Review
- Discovering functional interactions among schizophrenia-risk genes by combining behavioral genetics with cell biology.Neuroscience and biobehavioral reviews · 2024Review
- The involvement of KTranslational psychiatry · 2024Review
- Dysfunctional Parvalbumin Neurons in Schizophrenia and the Pathway to the Clinical Application of Kv3 Channel Modulators.International journal of molecular sciences · 2024Review
- The binding and mechanism of a positive allosteric modulator of Kv3 channels.Nature communications · 2024Article
- Kv3.1 Voltage-gated Potassium Channels Modulate Anxiety-like Behaviors in Female Mice.Neuroscience · 2024Article
- Cross-continental environmental and genome-wide association study on children and adolescent anxiety and depression.Frontiers in psychiatry · 2024Article
- Voltage-gated potassium channels as a potential therapeutic target for the treatment of neurological and psychiatric disorders.Frontiers in cellular neuroscience · 2024Review
- A cytoskeleton-membrane interaction conserved in fast-spiking neurons controls movement, emotion, and memory.Molecular psychiatry · 2023Article
- The effects of AUT00206, a novel Kv3.1/3.2 potassium channel modulator, on task-based reward system activation: a test of mechanism in schizophrenia.Psychopharmacology · 2022Article
- The effect of AUT00206, a Kv3 potassium channel modulator, on dopamine synthesis capacity and the reliability of [Journal of psychopharmacology (Oxford, England) · 2022Article
- Inhibitory Effectiveness in Delayed-Rectifier Potassium Current Caused by Vortioxetine, Known to Be a Novel Antidepressant.Biomedicines · 2022Article
- Valproate reverses mania-like behaviors in mice via preferential targeting of HDAC2.Molecular psychiatry · 2021Article
- The Neurometabolic Basis of Mood Instability: The Parvalbumin Interneuron Link-A Systematic Review and Meta-Analysis.Frontiers in pharmacology · 2021Review
- First Evidence of Kv3.1b Potassium Channel Subtype Expression during Neuronal Serotonergic 1C11 Cell Line Development.International journal of molecular sciences · 2020Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 4 countries.
Funding
Abstract
Kv3.1 and Kv3.2 voltage-gated potassium channels are expressed on parvalbumin-positive GABAergic interneurons in corticolimbic brain regions and contribute to high-frequency neural firing. The channels are also expressed on GABAergic neurons of the basal ganglia, substantia nigra, and ventral tegmental area (VTA) where they regulate firing patterns critical for movement control, reward, and motivation. Modulation of Kv3.1 and Kv3.2 channels may therefore have potential in the treatment of disorders in which these systems have been implicated, such as bipolar disorder. Following the recent development of a potassium channel modulator, AUT1-an imidazolidinedione compound that specifically increases currents mediated by Kv3.1 and Kv3.2 channels in recombinant systems-we report that the compound is able to reverse 'manic-like' behavior in two mouse models: amphetamine-induced hyperactivity and ClockΔ19 mutants. AUT1 completely prevented amphetamine-induced hyperactivity in a dose-dependent manner, similar to the atypical antipsychotic, clozapine. Similar efficacy was observed in Kv3.2 knockout mice. In contrast, AUT1 was unable to prevent amphetamine-induced hyperactivity in mice lacking Kv3.1 channels. Notably, Kv3.1-null mice displayed baseline hyperlocomotion, reduced anxiety-like behavior, and antidepressant-like behavior. In ClockΔ19 mice, AUT1 reversed hyperactivity. Furthermore, AUT1 application modulated firing frequency and action potential properties of ClockΔ19 VTA dopamine neurons potentially through network effects. Kv3.1 protein levels in the VTA of ClockΔ19 and WT mice were unaltered by acute AUT1 treatment. Taken together, these results suggest that the modulation of Kv3.1 channels may provide a novel approach to the treatment of bipolar mania.
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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.