Pharmacological evaluation of E2730, a novel selective uncompetitive GAT1 inhibitor, on epileptiform activities in resected brain tissues from human focal cortical dysplasia ex vivo.
Epilepsy Res
; 202: 107364, 2024 May.
Article
em En
| MEDLINE
| ID: mdl-38640591
ABSTRACT
Focal cortical dysplasia (FCD) is an important etiology of focal epilepsy in children and adults. However, only a few preclinical models sufficiently reproduce the characteristic histopathologic features of FCD. To improve the success rate of clinical trials for antiseizure medications (ASMs) in patients with FCD, more human-relevant preclinical models are needed, and epileptic foci resected from patients are a powerful tool for this purpose. Here, we conducted ex vivo studies using epileptic foci resected from patients with FCD type II to evaluate the pharmacologic effects of the ASM candidate E2730, a selective uncompetitive inhibitor of γ-aminobutyric acid transporter 1. We used the same ex vivo assay system to assess carbamazepine (CBZ), an ASM often prescribed for focal epilepsy, as a reference. At the higher dose tested (200⯵M), both E2730 and CBZ suppressed spontaneous epileptiform activities almost completely. At the lower dose (100⯵M), CBZ reduced the area of brain tissue showing epileptiform activity, whereas E2730 significantly decreased the number of epileptiforms. These findings suggest that E2730-both as a single agent and in combination with CBZ-merits evaluation in clinical trials involving patients with FCD.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas da Membrana Plasmática de Transporte de GABA
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Anticonvulsivantes
Limite:
Adult
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Child
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Child, preschool
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Female
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Humans
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Male
Idioma:
En
Revista:
Epilepsy Res
Assunto da revista:
CEREBRO
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NEUROLOGIA
Ano de publicação:
2024
Tipo de documento:
Article