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XB-ART-55839
Epilepsia 2018 Nov 01;5911:e172-e178. doi: 10.1111/epi.14578.
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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 , Holliman D , Mitchell P , Jenkins A , Chen PE , Walker MC , Williams RSB .


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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.

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