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Perampanel and decanoic acid show synergistic action against AMPA receptors and seizures

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. Green open access

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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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