Evidence map›Paper›PMID 26608744›Full record

ArticleBrain : a journal of neurology2016

Seizure control by decanoic acid through direct AMPA receptor inhibition.

Pishan Chang, Katrin Augustin, Kim Boddum, Sophie Williams, Min Sun, John A Terschak, Jörg D Hardege, Philip E Chen, Matthew C Walker, Robin S B Williams

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Brain : a journal of neurology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
124citing papers in PubMed, 2 pooled it
11.5field-weighted citation impact, top 1% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

124 citing papers in PubMed, 2 syntheses or guidelines pooled it, 227 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Trial
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Edible Safety Evaluation ofFoods (Basel, Switzerland) · 2025
    Article
  19. Review
  20. Article

64 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 1 country.

Pishan Chang1 Centre for Biomedical Sciences, School of Biological Sciences, Royal Holloway University of London, Egham, TW20 0EX, UK.
Katrin Augustin1 Centre for Biomedical Sciences, School of Biological Sciences, Royal Holloway University of London, Egham, TW20 0EX, UK.
Kim Boddum2 Department of Clinical and Experimental Epilepsy, Institute of Neurology, University College London, WC1N 3BG, UK.
Sophie Williams2 Department of Clinical and Experimental Epilepsy, Institute of Neurology, University College London, WC1N 3BG, UK.
Min Sun2 Department of Clinical and Experimental Epilepsy, Institute of Neurology, University College London, WC1N 3BG, UK.
John A Terschak3 School of Biological, Biomedical and Environmental Sciences, University of Hull, Cottingham Road, Hull HU6 7RX, UK.
Jörg D Hardege3 School of Biological, Biomedical and Environmental Sciences, University of Hull, Cottingham Road, Hull HU6 7RX, UK.
Philip E Chen1 Centre for Biomedical Sciences, School of Biological Sciences, Royal Holloway University of London, Egham, TW20 0EX, UK.
Matthew C Walker2 Department of Clinical and Experimental Epilepsy, Institute of Neurology, University College London, WC1N 3BG, UK m.walker@ucl.ac.uk robin.williams@rhul.ac.uk.
Robin S B Williams1 Centre for Biomedical Sciences, School of Biological Sciences, Royal Holloway University of London, Egham, TW20 0EX, UK m.walker@ucl.ac.uk robin.williams@rhul.ac.uk.
Royal Holloway University of London · GBUniversity College London · GBUniversity of Hull · GB

Funding

Department of HealthNational Centre for the Replacement, Refinement and Reduction of Animals in Research G0900775/1
6 · The paper itself

Abstract

The medium chain triglyceride ketogenic diet is an established treatment for drug-resistant epilepsy that increases plasma levels of decanoic acid and ketones. Recently, decanoic acid has been shown to provide seizure control in vivo, yet its mechanism of action remains unclear. Here we show that decanoic acid, but not the ketones β-hydroxybutryate or acetone, shows antiseizure activity in two acute ex vivo rat hippocampal slice models of epileptiform activity. To search for a mechanism of decanoic acid, we show it has a strong inhibitory effect on excitatory, but not inhibitory, neurotransmission in hippocampal slices. Using heterologous expression of excitatory ionotropic glutamate receptor AMPA subunits in Xenopus oocytes, we show that this effect is through direct AMPA receptor inhibition, a target shared by a recently introduced epilepsy treatment perampanel. Decanoic acid acts as a non-competitive antagonist at therapeutically relevant concentrations, in a voltage- and subunit-dependent manner, and this is sufficient to explain its antiseizure effects. This inhibitory effect is likely to be caused by binding to sites on the M3 helix of the AMPA-GluA2 transmembrane domain; independent from the binding site of perampanel. Together our results indicate that the direct inhibition of excitatory neurotransmission by decanoic acid in the brain contributes to the anti-convulsant effect of the medium chain triglyceride ketogenic diet.

Indexed as

AnimalsDecanoic AcidsFemaleHippocampusMaleOrgan Culture TechniquesProtein BindingProtein Structure, SecondaryRatsRats, Sprague-DawleyReceptors, AMPASeizuresXenopus laevisdecanoic acidDecanoic AcidsReceptors, AMPAAMPA receptorsdecanoic acidepilepsyketogenic dietseizure control

Identifiers

PMID26608744
PMCPMC4805082
OpenAlexW2181121996

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.