title: Propafenone enhances the anticonvulsant action of classical antiepileptic drugs in the mouse maximal electroshock model.
abstract: BACKGROUND
  Antiarrhythmic and antiepileptic drugs share some mechanisms of actions. Therefore, possibility of interactions between these in epileptic patients with cardiac arrhythmias is quite considerable. Herein, we attempted to assess interactions between propafenone and four conventional antiepileptic drugs: carbamazepine, valproate, phenytoin and phenobarbital.
  
  
  METHODS
  Effects of propafenone on seizures were determined in the electroconvulsive threshold test in mice. Interactions between propafenone and antiepileptic drugs were estimated in the model of maximal electroshock. Motor coordination was evaluated in the chimney test, while long-term memory in the passive-avoidance task. Brain concentrations of antiepileptics were determined by fluorescence polarization immunoassay.
  
  
  RESULTS
  Propafenone up to 50mg/kg did not affect the electroconvulsive threshold, significantly enhancing this parameter at doses of 60-90mg/kg. Applied at its subthreshold doses, propafenone potentiated the antielectroshock action of all four tested classical antiepileptics: carbamazepine, valproate, phenytoin, and phenobarbital. Propafenone alone and in combinations with antiepileptics impaired neither motor performance nor long-term memory in mice. Propafenone did not change brain concentration of phenytoin and phenobarbital; however, it significantly decreased brain levels of carbamazepine and increased those of valproate.
  
  
  CONCLUSIONS
  Propafenone exhibits its own anticonvulsant effect and enhances the action of classical antiepileptic drugs against electrically induced convulsions in mice. Further investigations are required to determine the effect of propafenone on antiepileptic therapy in humans.
authors.affiliation: Independent Unit of Experimental Neuropathophysiology, Department of Pathophysiology, Medical University of Lublin, Lublin, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Banach
authors.affiliation: Independent Unit of Experimental Neuropathophysiology, Department of Pathophysiology, Medical University of Lublin, Lublin, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Piskorska
authors.affiliation: Independent Unit of Experimental Neuropathophysiology, Department of Pathophysiology, Medical University of Lublin, Lublin, Poland. Electronic address: kinga.borowicz@umlub.pl.
authors.forename: Kinga K
authors.initials: KK
authors.lastname: Borowicz-Reutt
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000493:pharmacokinetics / Q000494:pharmacology; D001362:Avoidance Learning / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D002220:Carbamazepine / Q000493:pharmacokinetics / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004597:Electroshock; D008297:Male; D051379:Mice; D010634:Phenobarbital / Q000493:pharmacokinetics / Q000494:pharmacology*; D010672:Phenytoin / Q000493:pharmacokinetics / Q000494:pharmacology*; D011405:Propafenone / Q000493:pharmacokinetics / Q000494:pharmacology*; D014635:Valproic Acid / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D000927:Anticonvulsants; D002220:Carbamazepine; D014635:Valproic Acid; D010672:Phenytoin; D011405:Propafenone; D010634:Phenobarbital
keywords: Classical antiepileptic drugs; Electroshock maximal; Interactions; Propafenone