September 28, 2022

Lacosamide (Vimpat ®) Decreases Neonatal Seizures Without Increasing Apoptosis

Abstract found on Wiley Online Library

Objective: Many seizing neonates fail to respond to first-line anticonvulsant medications. Phenobarbital, an allosteric modulator of GABAA receptors, has low efficacy in treating neonatal seizures and causes neuronal apoptosis [cell death]. Yet, it is one of the most used anticonvulsants in this age group. In neonatal mice, phenobarbital’s poor effectiveness is due in part to high intraneuronal chloride concentration, which causes GABA to exert depolarizing actions. Therefore, another approach to treat neonatal seizures could be to use anticonvulsants that do not rely on GABAergic modulation. We evaluated if lacosamide decreases seizures in neonatal mice and if it increases apoptosis in vitro and in vivo.

Methods: In vitro, we measured the effect of different lacosamide concentrations on seizure-like activity induced by the pro-convulsant drug 4-aminopyridine in neocortical brain slices (layer IV/V) from neonatal (postnatal day P8-11) and adult (1-1.6-months-old) C57BL/6J mice. In vivo, we recorded the effect of different lacosamide concentrations on neonatal behavioral seizures induced by kainic acid. We studied neocortical apoptosis in vitro and in vivo, measuring TUNEL signal and cleaved-caspase 3.

Results: Lacosamide reduced epileptiform activity in neocortical brain slices of neonates and adults in a concentration-dependent manner. In vivo, lacosamide reduced the duration and number of behavioral seizures. Lacosamide did not increase total or neuronal apoptosis in the neocortex in vitro or in vivo.

Significance: Lacosamide reduces neocortical seizure-like activity in neonatal mice in vitro and in vivo without an acute increase in apoptosis. Our results support the use of lacosamide to treat neonatal seizures, with the advantage of not increasing apoptosis acutely.