Cenobamate suppresses seizures without inducing cell death in neonatal rats.
Epilepsy Behav
; 158: 109898, 2024 Sep.
Article
de En
| MEDLINE
| ID: mdl-39002273
ABSTRACT
GABA modulators such as phenobarbital (PB) and sodium channel blockers such as phenytoin (PHT) have long been the mainstay of pharmacotherapy for the epilepsies. In the context of neonatal seizures, both PB and PHT display incomplete clinical efficacy. Moreover, in animal models, neonatal exposure to these medications result in neurodegeneration raising concerns about safety. Cenobamate, a more recently approved medication, displays unique pharmacology as it is both a positive allosteric modulator of GABA-A receptors, and a voltage-gated sodium channel blocker. While cenobamate is approved for adult use, its efficacy and safety profile against neonatal seizures is poorly understood. To address this gap, we assessed the efficacy and safety of cenobamate in immature rodents. Postnatal day (P)7 rat pups were pretreated with cenobamate and challenged with the chemoconvulsant pentylenetetrazole (PTZ) to screen for anti-seizure effects. In a separate experiment, P7 rats were treated with cenobamate, and brains were processed to assess induction of cell death. Cenobamate displays dose-dependent anti-seizure efficacy in neonatal rats. Unlike PHB and PHT, it does not induce neurotoxicity in P7 rats. Thus, cenobamate may be effective at treating neonatal seizures while avoiding unwanted neurotoxic side effects such as cell death.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Crises épileptiques
/
Carbamates
/
Mort cellulaire
/
Rat Sprague-Dawley
/
Modèles animaux de maladie humaine
/
Relation dose-effet des médicaments
/
Animaux nouveau-nés
/
Anticonvulsivants
Limites:
Animals
Langue:
En
Journal:
Epilepsy Behav
Sujet du journal:
CIENCIAS DO COMPORTAMENTO
/
NEUROLOGIA
Année:
2024
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique