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

• Published in: Journal of Neural Transmission 2019-02, Vol.126 (2), p.115-122
• Main Authors: Sawicka, Katarzyna M., Wawryniuk, Agnieszka, Daniluk, Jadwiga, Karwan, Sławomir, Florek-Łuszczki, Magdalena, Chmielewski, Jarosław, Łuszczki, Jarogniew J.
• Format: Article
• Language: English
• Subjects: Medicine; Medicine & Public Health; Neurology; Neurology and Preclinical Neurological Studies - Original; Neurology and Preclinical Neurological Studies - Original Article; Neurosciences; Psychiatry
• ISSN: 0300-9564; 1435-1463
• DOI: 10.1007/s00702-018-1940-y

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