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Perampanel and decanoic acid show synergistic action against AMPA receptors and seizures
Author(s) -
Augustin Katrin,
Williams Sophie,
Cunningham Mark,
Devlin Anita M.,
Friedrich Maximilian,
Jayasekera Ashan,
Hussain Mohammed A.,
Holliman Damian,
Mitchell Patrick,
Jenkins Alistair,
Chen Philip E.,
Walker Matthew C.,
Williams Robin S.B.
Publication year - 2018
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.14578
Subject(s) - perampanel , decanoic acid , ampa receptor , pharmacology , epilepsy , chemistry , receptor , neuroscience , biochemistry , biology , glutamate receptor
Summary 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.