title: Synergistic Interaction of Retigabine with Levetiracetam in the Mouse Maximal Electroshock-Induced Seizure Model: A Type II Isobolographic Analysis.
abstract: OBJECTIVE
  To assess interactions between retigabine and levetiracetam in suppressing maximal electroshock-induced tonic seizures in Albino Swiss mice, type II isobolographic analysis was used. Total brain antiepileptic drug concentrations were measured with high pressure liquid chromatography.
  
  
  RESULTS
  The combinations of retigabine with levetiracetam at the fixed-ratios of 1:5 and 1:10 were supra-additive (synergistic; p < 0.05) in terms of seizure suppression, while the combinations at the fixed-ratios of 1:1 and 1:2 were additive. No pharmacokinetic changes in total brain concentrations of levetiracetam and retigabine were documented, indicating the pharmacodynamic nature of interaction between these antiepileptic drugs in the mouse maximal electroshock-induced tonic seizure model.
  
  
  CONCLUSIONS
  The combination of retigabine with levetiracetam at the fixed-ratios of 1:5 and 1:10 appears to be particularly beneficial combination exerting supra-additive interaction in suppressing maximal electroshock-induced tonic seizures.
authors.affiliation: Department of Pathophysiology, Medical University of Lublin, Lublin, Poland.
authors.forename: Jarogniew J
authors.initials: JJ
authors.lastname: Luszczki
authors.forename: Mirosław
authors.initials: M
authors.lastname: Zagaja
authors.forename: Barbara
authors.initials: B
authors.lastname: Miziak
authors.forename: Magdalena
authors.initials: M
authors.lastname: Florek-Luszczki
authors.forename: Stanislaw J
authors.initials: SJ
authors.lastname: Czuczwar
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002219:Carbamates / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004597:Electroshock; D000077287:Levetiracetam; D008297:Male; D051379:Mice; D015233:Models, Statistical; D010655:Phenylenediamines / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010889:Piracetam / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D012640:Seizures / Q000188:drug therapy*
chemical_list: D002219:Carbamates; D010655:Phenylenediamines; C101866:ezogabine; D000077287:Levetiracetam; D010889:Piracetam