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

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.

journal_name

Epilepsia

journal_title

Epilepsia

authors

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

doi

10.1111/epi.14578

subject

Has Abstract

pub_date

2018-11-01 00:00:00

pages

e172-e178

issue

11

eissn

0013-9580

issn

1528-1167

journal_volume

59

pub_type

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