ESLICARBAZEPINE ACETATE IS ANTIEPILEPTOGENIC IN THE LATRUNCULIN A MOUSE MODEL OF PARTIAL SEIZURES

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Although there are many drugs available which have powerful anticonvulsant activity, there is still a high unmet need for antiepileptogenic compounds that prevent the development of chronic epilepsy. Eslicarbazepine acetate (ESL) is a once‐daily (QD) antiepileptic drug (AED) that is converted extensively to eslicarbazepine (a voltage‐gated sodium channel and T‐type calcium channel blocker) after oral administration.1 ESL is a potent anticonvulsant in animal models. Latrunculin A is an actin depolymerization agent that promotes neurotransmitter release in hippocampal synapses and induces multiple action potential firing and increases action potential duration. Latrunculin A hippocampal microperfusion in freely moving mice induces acute epileptic seizures, followed by the occurrence of chronic sporadic spontaneous seizures, in association with changes in extracellular concentrations of excitatory and inhibitory amino acids.2 We have examined ESL for its potential antiepileptogenic activity in preventing the development of chronic partial seizures induced by latrunculin A microperfusion in the mouse hippocampus.Hippocampi of freely‐moving C57BL/6J male mice were continuously perfused with latrunculin A (8 μg/ml, 1 μl/min, 8h/day) for 72 hours. Sham animals received injections of artificial CSF. Forty‐eight‐hours after intrahippocampal latrunculin A infusion, mice were administered either vehicle, 75 mg/kg or 150 mg/kg ESL p.o. once‐daily for three consecutive days. CSF‐infused mice received vehicle. Body temperature and home‐cage locomotor behaviour were assessed four weeks after the end of ESL treatment. Cortical EEG monitoring by telemetry was performed once per week after the end of ESL treatment over a period of six weeks. Data is presented as means ± standard error of the mean (SEM). Data was analyzed using One‐ or Two‐way ANOVA followed by Holm‐Sidak's multiple comparisons test, as appropriate; planned comparison were performed between sham or vehicle (control) and ESL treated groups.Latrunculin A microperfusion in the mouse hippocampus induced electrographic seizures and discharges in the mouse. EEG monitoring showed that transitory ESL treatment within the epileptogenic period caused a sustained significant decrease in the frequency (42 and 74% decrease for 75 and 150 mg/kg ESL versus vehicle at week 4, respectively; 62 and 72% decrease for 75 and 150 mg/kg ESL versus vehicle at week 6, respectively) of epileptiform discharges. There were no significant differences between the two doses of ESL used. Latrunculin A microperfusion and transitory ESL treatment induced no changes in body temperature and locomotor activity, as assessed on week 4 after latrunculin A administration.Transitory oral ESL treatment attenuated sporadic spontaneous electrographic seizures and discharges induced by latrunculin A microperfusion in the mouse hippocampus, supporting a possible anti‐epileptogenic effect of ESL.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.