Perampanel appears to be effective for the prevention of early/life seizures in Dravet syndrome (DS) mouse models with fever-induced seizures, according to a recently published study in Epilepsy and Behaviour.
Early-life epileptic syndromes are typically associated with resistance to treatment despite the development of new-generation antiepileptic medication. Research has shown that the expression and function of several therapeutic targets for epilepsy change at different ages.
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“Neonatal seizures remain highly refractory to conventional treatment, and perinatal asphyxia and neonatal hypoxic encephalopathy are the most common cause of refractory neonatal seizures,” the authors wrote.
Several studies have revealed that the AMPAR subtype of the glutamate receptor has a higher expression in the cortical and limbic principal neurons of the perinatal brain and could play a major role in the development of early/life seizures, the researchers noted. Furthermore, there is increasing evidence that GABAAR agonists and NMDAR antagonists lead to neuron and oligodendrocyte apoptosis in perinatal brains in animal models; however, they remain the first line of treatment for early/life seizures, they added.
Therefore, the authors aimed to assess the efficacy of perampanel, a non/competitive AMPAR inhibitor, in 2 early-life seizure animal models.
The study used hypoxia-induced seizures in the neonatal rats model and hyperthermia-induced seizures in the Dravet syndrome mice model. In the former, perampanel was administered through an intraperitoneal injection 30 minutes before the induction of hypoxia; in the latter, perampanel was administered orally an hour before the induction of hyperthermia.
A comparison between animals that received perampanel and a control group revealed that in both animal models, perampanel led to reduced seizure counts, reduced cumulative seizure duration, and increased seizure latency. Lower doses did decrease seizure counts and cumulative seizure duration but had almost no effect on seizure latency.
“Furthermore, we provide additional evidence to already mounting support for the use of perampanel in Dravet syndrome patients to decrease the susceptibility to febrile seizures, which are often drug-resistant and a high risk of sudden death,” the authors suggest.
Roberts NS, Handy MJ, Ito Y, Hashimoto K, Jensen FE, Talos DM. Anti-seizure efficacy of perampanel in two established rodent models of early-life epilepsy. Epilepsy Behav. Published online April 27, 2023;143:109194. doi:10.1016/j.yebeh.2023.109194