@article{69a5fcb448d14ff7bc6ac7244baf7438,
title = "The AMPA receptor antagonist perampanel suppresses epileptic activity in human focal cortical dysplasia",
abstract = "Focal cortical dysplasia (FCD) is one of the most common malformations causing refractory epilepsy. Dysregulation of glutamatergic systems plays a critical role in the hyperexcitability of dysplastic neurons in FCD lesions. The pharmacoresistant nature of epilepsy associated with FCD may be due to a lack of well-tolerated and precise antiepileptic drugs that can target glutamate receptors. Here, for the first time in human FCD brain slices, we show that the established, noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, perampanel has potent antiepileptic action. Moreover, we demonstrate that this effect is due to a reduction in burst firing behavior in human FCD microcircuits. These data support a potential role for the treatment of refractory epilepsy associated with FCD in human patients.",
keywords = "AMPA, epilepsy, focal cortical dysplasia, glutamate, perampanel",
author = "{Brito da Silva}, Anderson and Jane Pennifold and Ben Henley and Koustav Chatterjee and David Bateman and Whittaker, {Roger W.} and Abhijit Joshi and Hrishikesh Kumar and Claire Nicholson and Baker, {Mark R.} and Greenhill, {Stuart D.} and Richard Walsh and Stefano Seri and Jones, {Roland S.G.} and Woodhall, {Gavin L.} and Mark O Cunningham",
note = "Funding Information: This work has been supported by investigator‐initiated grants from Eisai (MOC and GLW), Birmingham Children's Hospital Charities grant BCHRF349 (SS, GLW) and Aston Brain Centre (GLW), the Wellcome Trust/EPSRC (102037; RGW and MOC), and a CAPES‐funded (Brazil) PhD studentship (BEX‐0437‐14‐0; ABDS, RGW, and MOC). Editorial support, under the direction of the authors, was provided by Stephanie Agbu, PhD, of CMC AFFINITY, a division of Complete Medical Communications Inc, Hackensack, NJ, USA, funded by Eisai Inc, in accordance with Good Publication Practice (GPP3) guidelines. Funding Information: This work has been supported by investigator-initiated grants from Eisai (MOC and GLW), Birmingham Children's Hospital Charities grant BCHRF349 (SS, GLW) and Aston Brain Centre (GLW), the Wellcome Trust/EPSRC (102037; RGW and MOC), and a CAPES-funded (Brazil) PhD studentship (BEX-0437-14-0; ABDS, RGW, and MOC). Editorial support, under the direction of the authors, was provided by Stephanie Agbu, PhD, of CMC AFFINITY, a division of Complete Medical Communications Inc, Hackensack, NJ, USA, funded by Eisai Inc, in accordance with Good Publication Practice (GPP3) guidelines. Publisher Copyright: {\textcopyright} 2021 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.",
year = "2022",
month = sep,
day = "30",
doi = "10.1002/epi4.12549",
language = "English",
volume = "7",
pages = "488--495",
journal = "Epilepsia Open",
issn = "2470-9239",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "3",
}