Purpose: The antiepileptic drug, lacosamide, exerts its therapeutic activity by enhancing slow inactivation of voltage-gated sodium channels. Because putative preventive or disease-modifying effects of drugs may affect epileptogenesis, intrinsic severity, and comorbidities, it is of particular interest to assess the effect of lacosamide on the development of epilepsy and associated cellular alterations.
Methods: The effect of lacosamide was evaluated in an electrical rat status epilepticus (SE) model with a 24-day treatment phase following induction of SE. The impact of lacosamide on the development of spontaneous seizures based on continuous video-electroencephalography (EEG) monitoring, as well as the impact on neuronal cell loss and alterations in hippocampal neurogenesis, was assessed.
Key findings: Neither low-dose nor high-dose lacosamide affected the development of spontaneous seizures. A dose-dependent neuroprotective effect of lacosamide with significant reduction of neuronal cell loss was observed in the hippocampal CA1 region, as well as in the piriform cortex. In addition, lacosamide attenuated the impact of SE on the rate of hippocampal cell neurogenesis. Moreover, lacosamide prevented a significant rise in the number of persistent basal dendrites.
Significance: Our data do not support an antiepileptogenic effect of lacosamide. However, because lacosamide reduced SE-associated cellular alterations, it would be of interest to determine whether these effects indicate a putative disease-modifying effect of lacosamide in future studies.
Keywords: Antiepileptic drug; Epilepsy; Hippocampus; Lacosamide; Neuroprotection; Sodium channel.
Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.