PURPOSE: Eslicarbazepine acetate (ESL, BIA 2-093) is a novel antiepileptic drug endowed with an anticonvulsant potency similar to that of carbamazepine, and shares with carbamazepine and oxcarbazepine the capability to inhibit voltage-gated sodium channels. ESL is efficacious against maximal electroshock seizure-induced seizures, protects against picrotoxin-induced seizures in mice and rats, and prevents development of kindling in rats. In vivo, latrunculin A microperfusion in the rat hippocampus induces acute epileptic seizures and long-term biochemical changes leading to decreased picrotoxin seizure threshold and spontaneous seizures. We have tested the effect of ESL on latrunculin A-induced seizures, and its effect on the changes in extracellular amino acid levels induced by latrunculin A. METHODS: Rat hippocampus was continuously perfused with a latrunculin A solution (4 microM) through CMA/12 microdialysis probes at a flow rate of 2 microl/min during 8 h with continuous EEG and videotape recording for 3 consecutive days. The same protocol was repeated after oral administration of ESL (3, 10 and 30 mg/kg). Samples from the microdialysate were collected and analyzed by HPLC using pre-column derivatization with 6 aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) and fluorescence detection. RESULTS: After the administration of 3 mg/kg of ESL, seizures were completely suppressed in the 66.7% of the rats. 10 and 30 mg/kg of ESL did completely suppressed seizures in the 100% of the animals studied. Hippocampal extracellular levels of glutamate, glycine and aspartate were significantly increased during latrunculin A microperfusion, while GABA levels remained unchanged. At the doses studied, ESL reversed the increases in extracellular glutamate and aspartate concentrations to basal levels and significantly reduced glycine levels. CONCLUSIONS: ESL, at oral doses of 3, 10 and 30 mg/kg, shows an excellent anticonvulsant effect against seizures induced by latrunculin A microperfusion in the rat, and prevents the increases in glutamate and aspartate induced by latrunculin A.
PURPOSE:Eslicarbazepine acetate (ESL, BIA 2-093) is a novel antiepileptic drug endowed with an anticonvulsant potency similar to that of carbamazepine, and shares with carbamazepine and oxcarbazepine the capability to inhibit voltage-gated sodium channels. ESL is efficacious against maximal electroshock seizure-induced seizures, protects against picrotoxin-induced seizures in mice and rats, and prevents development of kindling in rats. In vivo, latrunculin A microperfusion in the rat hippocampus induces acute epilepticseizures and long-term biochemical changes leading to decreased picrotoxinseizure threshold and spontaneous seizures. We have tested the effect of ESL on latrunculin A-induced seizures, and its effect on the changes in extracellular amino acid levels induced by latrunculin A. METHODS:Rat hippocampus was continuously perfused with a latrunculin A solution (4 microM) through CMA/12 microdialysis probes at a flow rate of 2 microl/min during 8 h with continuous EEG and videotape recording for 3 consecutive days. The same protocol was repeated after oral administration of ESL (3, 10 and 30 mg/kg). Samples from the microdialysate were collected and analyzed by HPLC using pre-column derivatization with 6 aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) and fluorescence detection. RESULTS: After the administration of 3 mg/kg of ESL, seizures were completely suppressed in the 66.7% of the rats. 10 and 30 mg/kg of ESL did completely suppressed seizures in the 100% of the animals studied. Hippocampal extracellular levels of glutamate, glycine and aspartate were significantly increased during latrunculin A microperfusion, while GABA levels remained unchanged. At the doses studied, ESL reversed the increases in extracellular glutamate and aspartate concentrations to basal levels and significantly reduced glycine levels. CONCLUSIONS:ESL, at oral doses of 3, 10 and 30 mg/kg, shows an excellent anticonvulsant effect against seizures induced by latrunculin A microperfusion in the rat, and prevents the increases in glutamate and aspartate induced by latrunculin A.
Authors: Germán Sierra-Paredes; Ana I Loureiro; Lyndon C Wright; Germán Sierra-Marcuño; Patrício Soares-da-Silva Journal: BMC Neurosci Date: 2014-12-20 Impact factor: 3.288