Effect of eslicarbazepine acetate (BIA 2-093) on latrunculin A-induced seizures and extracellular amino acid concentrations in the rat hippocampus.
OBJECTIVE
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.
Sierra-Paredes
Germán
G
Neuroscience Division, Department of Biochemistry and Molecular Biology, School of Medicine, University of Santiago, San Francisco 1, 15782 Santiago de Compostela, Spain. bngersp@usc.es
Oreiro-García
Maria Teresa
MT
Vázquez-Illanes
Maria Dolores
MD
Sierra-Marcuño
Germán
G
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002851:Chromatography, High Pressure Liquid; D003984:Dibenzazepines / Q000494:pharmacology*; D004569:Electroencephalography; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007202:Indicators and Reagents; D008297:Male; D008387:Marine Toxins; D017551:Microdialysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced* / Q000188:drug therapy*; D053778:Thiazolidines
D000596:Amino Acids; D000927:Anticonvulsants; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003984:Dibenzazepines; D007202:Indicators and Reagents; D008387:Marine Toxins; D053778:Thiazolidines; C416835:eslicarbazepine acetate; C037067:latrunculin A