1. Academic Validation
  2. Influence of dronedarone (a class III antiarrhythmic drug) on the anticonvulsant potency of four classical antiepileptic drugs in the tonic-clonic seizure model in mice

Influence of dronedarone (a class III antiarrhythmic drug) on the anticonvulsant potency of four classical antiepileptic drugs in the tonic-clonic seizure model in mice

  • J Neural Transm (Vienna). 2019 Feb;126(2):115-122. doi: 10.1007/s00702-018-1940-y.
Katarzyna M Sawicka 1 2 Agnieszka Wawryniuk 1 Jadwiga Daniluk 1 3 Sławomir Karwan 4 Magdalena Florek-Łuszczki 5 Jarosław Chmielewski 6 Jarogniew J Łuszczki 7 8
Affiliations

Affiliations

  • 1 Department of Internal Medicine in Nursing, Medical University of Lublin, Lublin, Poland.
  • 2 Department of Pathophysiology, Medical University of Lublin, Lublin, Poland.
  • 3 Pope John Paul II State School of Higher Education in Biala Podlaska, Biala Podlaska, Poland.
  • 4 Regional Specialized Children's Hospital, Olsztyn, Poland.
  • 5 Department of Medical Anthropology, Institute of Rural Health, Lublin, Poland.
  • 6 Institute of Environmental Protection-National Research Institute in Warsaw, Warsaw, Poland.
  • 7 Department of Pathophysiology, Medical University of Lublin, Lublin, Poland. jarogniew.luszczki@umlub.pl.
  • 8 Isobolographic Analysis Laboratory, Institute of Rural Health, Lublin, Poland. jarogniew.luszczki@umlub.pl.
Abstract

Increasing evidence indicates that some antiarrhythmic drugs play a pivotal role in seizures, not only in vivo studies on Animals, but also in clinical trials. Some of these antiarrhythmic drugs potentiate or alleviate the anticonvulsant action of the classical antiepileptic drugs. The aim of this study was to determine the influence of dronedarone (DRO-a multichannel blocker belonging to the class III of antiarrhythmic drugs) on the anticonvulsant effects of four standard antiepileptic drugs (carbamazepine, phenobarbital, phenytoin and valproate) in the tonic-clonic seizure model in mice. Potential acute adverse effects exerted by the antiepileptic drugs combined with DRO were evaluated in three behavioral tests (chimney, grip-strength and passive avoidance). To confirm the nature of interaction, total brain concentrations of antiepileptic drugs were measured. DRO (50 mg/kg, i.p.) significantly reduces the anticonvulsant potency of phenytoin (P < 0.05), having no impact on that of carbamazepine, phenobarbital and valproate in the tonic-clonic seizure model in mice. DRO (50 mg/kg) neither changed total brain concentrations of phenytoin in mice, nor affected normal behavior in experimental Animals subjected to the chimney, grip-strength and passive avoidance tests. In conclusion, DRO should not be combined with phenytoin because it reduced the anticonvulsant effects of the latter drug in experimental Animals. The combined administration of DRO with carbamazepine, phenobarbital and valproate resulted in neutral interaction between these drugs in the tonic-clonic seizure model in mice.

Keywords

Antiarrhythmic drugs; Antiepileptic drugs; Dronedarone; Drug interactions.

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