3 research outputs found
Effects of eslicarbazepine acetate on acute and chronic latrunculin A-induced seizures and extracellular amino acid levels in the mouse hippocampus
Background: Latrunculin A microperfusion of the hippocampus induces acute epileptic seizures and long-term
biochemical changes leading to spontaneous seizures. This study tested the effect of eslicarbazepine acetate (ESL),
a novel antiepileptic drug, on latrunculin A-induced acute and chronic seizures, and changes in brain amino acid
extracellular levels. Hippocampi of Swiss mice were continuously perfused with a latrunculin A solution (4 ÎĽM, 1 ÎĽl/min,
7 h/day) with continuous EEG and videotape recording for 3 consecutive days. Microdialysate samples were analyzed
by HPLC and fluorescence detection of taurine, glycine, aspartate, glutamate and GABA. Thereafter, mice were
continuously video monitored for two months to identify chronic spontaneous seizures or behavioral changes.
Control EEG recordings (8 h) were performed in all animals at least once a week for a minimum of one month.
Results: Oral administration of ESL (100 mg/kg), previous to latrunculin A microperfusion, completely prevented
acute latrunculin A-induced seizures as well as chronic seizures and all EEG chronic signs of paroxysmal activity.
Hippocampal extracellular levels of taurine, glycine and aspartate were significantly increased during latrunculin A
microperfusion, while GABA and glutamate levels remained unchanged. ESL reversed the increases in extracellular
taurine, glycine and aspartate concentrations to basal levels and significantly reduced glutamate levels. Plasma
and brain bioanalysis showed that ESL was completely metabolized within 1 h after administration to mainly
eslicarbazepine, its major active metabolite.
Conclusion: ESL treatment prevented acute latrunculin A-induced seizures as well as chronic seizures and all EEG
chronic signs of paroxysmal activity, supporting a possible anti-epileptogenic effect of ESL in mice.This study was sponsored by BIAL – Portela & Cª, S.A.S