ArticleNature communications2018
Ancient and modern anticonvulsants act synergistically in a KCNQ potassium channel binding pocket.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03934268 (A Cohort Study on the Prognosis of Neonatal KCNQ2 Gene-associated Epileptic Encephalopathy), which is not on this map. Cited by 25 papers.
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.
A Cohort Study on the Prognosis of Neonatal KCNQ2 Gene-associated Epileptic Encephalopathy
Who cites it
25 citing papers in PubMed, 40 citations in OpenAlex.
- Polypharmacology of anthelmintics at host and parasite ion channels.PLoS pathogens · 2026Article
- HBasic research in cardiology · 2025Article
- Discovery of a potent, Kv7.3-selective potassium channel opener from a Polynesian traditional botanical anticonvulsant.Communications chemistry · 2024Article
- Polymodal KCommunications biology · 2024Article
- Phytotherapeutic options for the treatment of epilepsy: pharmacology, targets, and mechanism of action.Frontiers in pharmacology · 2024Review
- KJournal of pain research · 2024Article
- Ancient medicinal plant rosemary contains a highly efficacious and isoform-selective KCNQ potassium channel opener.Communications biology · 2023Article
- Native American ataxia medicines rescue ataxia-linked mutant potassium channel activity via binding to the voltage sensing domain.Nature communications · 2023Article
- Effect of Aerobic Exercise on Intestinal Microbiota with Amino Acids and Short-Chain Fatty Acids in Methamphetamine-Induced Mice.Metabolites · 2023Article
- Dual regulation of Kv7.2/7.3 channels by long-chain n-alcohols.The Journal of general physiology · 2023Article
- KCNQ5 activation by tannins mediates vasorelaxant effects of barks used in Native American botanical medicine.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Cannabidiol activates neuronal Kv7 channels.eLife · 2022Article
- KCNQ Potassium Channels as Targets of Botanical Folk Medicines.Annual review of pharmacology and toxicology · 2022Review
- Physiology and Therapeutic Potential of SK, H, and M Medium AfterHyperPolarization Ion Channels.Frontiers in molecular neuroscience · 2021Review
- Peripheral Voltage-Gated Cation Channels in Neuropathic Pain and Their Potential as Therapeutic Targets.Frontiers in pain research (Lausanne, Switzerland) · 2021Review
- KCNQ and KCNE Isoform-Dependent Pharmacology Rationalizes Native American Dual Use of Specific Plants as Both Analgesics and Gastrointestinal Therapeutics.Frontiers in physiology · 2021Article
- Combining endocannabinoids with retigabine for enhanced M-channel effect and improved KV7 subtype selectivity.The Journal of general physiology · 2020Article
- The ubiquitous flavonoid quercetin is an atypical KCNQ potassium channel activator.Communications biology · 2020Article
- Molecular Mechanisms and Structural Basis of Retigabine Analogues in Regulating KCNQ2 Channel.The Journal of membrane biology · 2020Article
- KCNQs: Ligand- and Voltage-Gated Potassium Channels.Frontiers in physiology · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Epilepsy has been treated for centuries with herbal remedies, including leaves of the African shrub Mallotus oppositifolius, yet the underlying molecular mechanisms have remained unclear. Voltage-gated potassium channel isoforms KCNQ2-5, predominantly KCNQ2/3 heteromers, underlie the neuronal M-current, which suppresses neuronal excitability, protecting against seizures. Here, in silico docking, mutagenesis and cellular electrophysiology reveal that two components of M. oppositifolius leaf extract, mallotoxin (MTX) and isovaleric acid (IVA), act synergistically to open neuronal KCNQs, including KCNQ2/3 channels. Correspondingly, MTX and IVA combine to suppress pentylene tetrazole-induced tonic seizures in mice, whereas individually they are ineffective. Co-administering MTX and IVA with the modern, synthetic anticonvulsant retigabine creates a further synergy that voltage independently locks KCNQ2/3 open. Leveraging this synergy, which harnesses ancient and modern medicines to exploit differential KCNQ isoform preferences, presents an approach to developing safe yet effective anticonvulsants.
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What OpenQuestion holds
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.