Interactions of retigabine with topiramate in the mouse tonic-clonic seizure model and chimney test – an isobolographic analysis

Robert Chmura 3,  
Jarogniew J. Łuszczki 2, 1  ,  
Isobolographic Analysis Laboratory, Institute of Rural Health, Jaczewskiego 2, PL 20-950 Lublin, Poland
Department of Pathophysiology, Medical University of Lublin, Jaczewskiego 8b, PL 20-090 Lublin, Poland
Department of Biostatistics, Demography and Epidemiology, Institute of Rural Health, Jaczewskiego 2, PL 20-950 Lublin, Poland
JPCCR 2017;11(1):61–65
Nowadays, one of the treatment options for patients with refractory epilepsy is polytherapy with two or more antiepileptic drugs (AEDs). Retigabine (RTG) is a novel third-generation AED with unique molecular mechanisms of action that has recently been approved as an add-on drug for the treatment of tonic-clonic seizures. To characterize types of interactions between RTG and topiramate (TPM – a second-generation AED), the maximal electroshock- induced seizure model (MES) and chimney test in mice were used.

Material and methods:
In the MES model, the anticonvulsant effects of the drugs in terms of suppression of tonic-clonic seizures in male albino Swiss mice were assessed. In the chimney test, the acute neurotoxic effects of the drugs with respect to impairment of motor coordination were determined. Type I isobolographic analysis for the combination of RTG and TPM was applied to assess the anticonvulsant and neurotoxic effects in both the MES and chimney tests. Total brain concentrations of RTG and TPM were measured to exclude any pharmacokinetic interaction between drugs.

The type I isobolographic analysis of interaction revealed that the combination of RTG with TPM produced additive interaction in the MES test and additivity, with a slight tendency towards antagonism in terms of acute neurotoxic effects in the chimney test. Neither RTG nor TPM mutually affected total brain concentrations in the experimental animals

The isobolographically analyzed combination of RTG with TPM is favourable and may be recommended to some patients with refractory epilepsy

Jarogniew J. Łuszczki   
Department of Pathophysiology, Medical University of Lublin, Jaczewskiego 8b, PL 20-090 Lublin, Poland, Department of Pathophysiology, Jaczewskiego 8, 20-090 Lublin, Poland
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