title: Effect of eslicarbazepine acetate in the corneal kindling progression and the amygdala kindling model of temporal lobe epilepsy.
abstract: OBJECTIVE
  The present study was aimed at determining the effect of eslicarbazepine acetate (ESL), eslicarbazepine and (R)-licarbazepine administration in the mouse corneal kindling and amygdala kindling models.
  
  
  METHODS
  NMRI mice were kindled by bilateral corneal stimulation twice daily. In amygdala kindling, mice were stimulated once daily via an implanted depth electrode until 10 generalized seizures were elicited. Maximal electroshocks (MES) were administered via corneal electrodes.
  
  
  RESULTS
  The average number of stimulations to reach a fully kindled generalized seizure was markedly increased by ESL. Administration of eslicarbazepine also inhibited the acquisition of kindling, whereas administration of R-licarbazepine did not affect the number of stimulations necessary to induce a specific seizure stage, and did not exert any relevant effect on mean seizure severity during kindling progression. ESL dose-dependently increased the focal seizure threshold and reduced seizure severity in amygdala kindling. Whereas eslicarbazepine treatment increased the afterdischarge threshold in a significant manner, (R)-licarbazepine treatment failed to exert a significant effect on thresholds in fully kindled mice. Administration of ESL and of eslicarbazepine significantly protected mice against MES-induced seizures, whereas that of (R)-licarbazepine failed to provide protection.
  
  
  CONCLUSIONS
  These data provide evidence of the anticonvulsant effect of ESL and its active metabolite eslicarbazepine on partial-onset seizures in corneal and amygdala kindling models. Based on an effect of the parent compound and the active metabolite eslicarbazepine, ESL treatment may not merely suppress seizure activity but may also provide a disease-modifying or antiepileptogenic effect. Future studies will be necessary to further evaluate a putative preventive effect, in particular when considering that re-stimulation following wash-out did not indicate a persistent effect. The findings reported here raise doubts on the contribution of (R)-licarbazepine as an active anticonvulsant.
authors.affiliation: Institute of Pharmacology, Toxicology, and Pharmacy, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Heidrun
authors.initials: H
authors.lastname: Potschka
authors.affiliation: Institute of Pharmacology, Toxicology, and Pharmacy, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Jonna
authors.initials: J
authors.lastname: Soerensen
authors.affiliation: Institute of Pharmacology, Toxicology, and Pharmacy, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Anton
authors.initials: A
authors.lastname: Pekcec
authors.affiliation: Department of Research and Development, BIAL - Portela & Cª, S.A., S. Mamede do Coronado, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Loureiro
authors.affiliation: Department of Research and Development, BIAL - Portela & Cª, S.A., S. Mamede do Coronado, Portugal; Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal. Electronic address: psoares.silva@bial.com.
authors.forename: Patrício
authors.initials: P
authors.lastname: Soares-da-Silva
mesh_terms: D000679:Amygdala / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use*; D003315:Cornea / Q000187:drug effects* / Q000502:physiology; D003984:Dibenzazepines / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004833:Epilepsy, Temporal Lobe / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D007696:Kindling, Neurologic / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice
chemical_list: D000927:Anticonvulsants; D003984:Dibenzazepines; C416835:eslicarbazepine acetate
keywords: (R)-licarbazepine; Amygdala kindling; Anticonvulsant drugs; Corneal kindling; Eslicarbazepine; Eslicarbazepine acetate