Augustin, K;
Williams, S;
Cunningham, M;
Devlin, AM;
Friedrich, M;
Jayasekera, A;
Hussain, MA;
... Williams, RSB; + view all
(2018)
Perampanel and decanoic acid show synergistic action against AMPA receptors and seizures.
Epilepsia
, 59
(11)
e172-e178.
10.1111/epi.14578.
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Abstract
Perampanel is an adjunctive treatment for epilepsy that works through the direct inhibition of AMPA receptors. The same molecular mechanism has recently been shown for a fatty acid, decanoic acid, prescribed in the medium chain triglyceride ketogenic diet for the treatment of patients with drug-resistant epilepsy. Because each compound has been proposed to act through a distinct AMPA receptor binding site, we predicted that perampanel and decanoic acid would act synergistically against AMPA receptors and, consequently, seizures. Here, we show a synergistic interaction between perampanel and decanoic acid in direct AMPA receptor inhibition, in an ex vivo model of seizure activity, and against seizure-induced activity in human brain slices. These data support a potential role for combination treatment using perampanel and dietary decanoic acid to provide enhanced seizure control.
| Type: | Article |
|---|---|
| Title: | Perampanel and decanoic acid show synergistic action against AMPA receptors and seizures |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1111/epi.14578 |
| Publisher version: | http://dx.doi.org/10.1111/epi.14578 |
| Language: | English |
| Additional information: | This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. © 2018 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy. |
| Keywords: | AMPA receptors, decanoic acid, drug-resistant epilepsy, perampanel, synergy |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Experimental Epilepsy |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10059596 |
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