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

Lookup NU author(s): Mark Cunningham, Dr Anita Devlin, Patrick Mitchell, Dr Alistair Jenkins

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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).


Abstract

© 2018 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy. 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.


Publication metadata

Author(s): Augustin K, Williams S, Cunningham M, Devlin AM, Friedrich M, Jayasekera A, Hussain MA, Holliman D, Mitchell P, Jenkins A, Chen PE, Walker MC, Williams RSB

Publication type: Article

Publication status: Published

Journal: Epilepsia

Year: 2018

Pages: Epub ahead of print

Online publication date: 15/10/2018

Acceptance date: 17/09/2018

ISSN (print): 0013-9580

ISSN (electronic): 1528-1167

Publisher: Wiley-Blackwell

URL: https://doi.org/10.1111/epi.14578

DOI: 10.1111/epi.14578


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