Effect of eslicarbazepine acetate (BIA 2-093) on latrunculin A-induced seizures and extracellular amino acid concentrations in the rat hippocampus.

Abstract

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.

• Authors: Germán Sierra-Paredes, Maria Teresa Oreiro-García, Maria Dolores Vázquez-Illanes, Germán Sierra-Marcuño
• Journal: Epilepsy research (Epilepsy Res) Vol. 77 Issue 1 Pg. 36-43 (Oct 2007) ISSN: 0920-1211 [Print] Netherlands
• PMID: 17890056 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amino Acids
• Anticonvulsants
• Bridged Bicyclo Compounds, Heterocyclic
• Dibenzazepines
• Indicators and Reagents
• Marine Toxins
• Thiazolidines
• eslicarbazepine acetate
• latrunculin A

Topics

• Amino Acids (metabolism)
• Animals
• Anticonvulsants (pharmacology)
• Brain Chemistry (drug effects)
• Bridged Bicyclo Compounds, Heterocyclic
• Chromatography, High Pressure Liquid
• Dibenzazepines (pharmacology)
• Electroencephalography
• Extracellular Space (drug effects, metabolism)
• Hippocampus (drug effects, metabolism)
• Indicators and Reagents
• Male
• Marine Toxins
• Microdialysis
• Rats
• Rats, Sprague-Dawley
• Seizures (chemically induced, drug therapy)
• Thiazolidines