| First Author | Roberts NS | Year | 2023 |
| Journal | Epilepsy Behav | Volume | 143 |
| Pages | 109194 | PubMed ID | 37119576 |
| Mgi Jnum | J:348514 | Mgi Id | MGI:7642097 |
| Doi | 10.1016/j.yebeh.2023.109194 | Citation | Roberts NS, et al. (2023) Anti-seizure efficacy of perampanel in two established rodent models of early-life epilepsy. Epilepsy Behav 143:109194 |
| abstractText | Early-life seizures can be refractory to conventional antiseizure medications (ASMs) and can also result in chronic epilepsy and long-term behavioral and cognitive deficits. Treatments targeting age-specific mechanisms contributing to epilepsy would be of clinical benefit. One such target is the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subtype of excitatory glutamate receptor, which is upregulated in the developing brain. Perampanel is a non-competitive, selective AMPAR antagonist that is FDA-approved for focal onset seizures (FOS) or primary generalized tonic-clonic seizures (PGTC) in children and adults. However, the efficacy of perampanel treatment in epilepsy patients younger than 4 years has been less documented. We thus tested the efficacy of perampanel in two early-life seizure models: (1) a rat model of hypoxia-induced neonatal seizures and (2) a mouse model of Dravet syndrome with hyperthermia-induced seizures. Pretreatment with perampanel conferred dose-dependent protection against early-life seizures in both experimental models. These findings suggest that AMPAR-mediated hyperexcitability could be involved in the pathophysiology of early-life seizures, which may be amenable to treatment with perampanel. |
