Effect of eslicarbazepine acetate (BIA 2-093) on latrunculin A-induced seizures and extracellular amino acid concentrations in the rat hippocampus.
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.[1]References
- Effect of eslicarbazepine acetate (BIA 2-093) on latrunculin A-induced seizures and extracellular amino acid concentrations in the rat hippocampus. Sierra-Paredes, G., Oreiro-García, M.T., Vázquez-Illanes, M.D., Sierra-Marcuño, G. Epilepsy Res. (2007) [Pubmed]
Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenesOpen Access LicencePrivacy PolicyTerms of Useapsburg
