Epilepsia · 2018
Perampanel and decanoic acid show synergistic action against AMPA receptors and seizures.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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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
Аннотация
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.