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

Figures

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  Fig. 1. Influence of dronedarone (DRO) on the threshold for maximal electroconvulsions in mice. Left panel graph illustrates current intensity–response function for tonic hind limb extension in the threshold test for maximal electroconvulsions in mice for DRO (a). The drug was administered i.p., at 120 min. before electroconvulsions. Data points indicate percentage of animals with seizures (n = 8 mice/data point). Right panel columns illustrate median current strength values (CS50 in mA ± S.E.M.) for DRO (b), required to produce tonic hind limb extension in 50% of animals tested. Log-probit method allowed calculation of the CS50 values, which were statistically analyzed with one-way ANOVA followed by the post-hoc Tukey–Kramer test. *P < 0.05 and ***P < 0.001 vs. the respective control (DRO 0) group

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  Fig. 2. Effect of dronedarone (DRO) on the protective activity of carbamazepine (CBZ), phenobarbital (PB), phenytoin (PHT) and valproate (VPA) in the tonic–clonic seizure model in mice. Left panel graphs illustrate dose–response functions (sigmoidal curves) for the anticonvulsant activity of classical antiepileptic drugs [CBZ (a), PB (c), PHT (e) and VPA (g)] alone and in combination with DRO in the tonic–clonic seizure model. Each data point reflects percent of mice protected (n = 8 mice/data point) from the tonic–clonic seizure model at a given dose (in mg/kg). Points of intersections with the dashed line at 50% reflect approximate ED50 values of antiepileptic drugs administered alone and in combination with DRO. Right panel columns illustrate median effective doses (ED50 in mg/kg ± S.E.M.) of antiepileptic drugs [CBZ (b), PB (d), PHT (f) and VPA (h)] that protected half of the tested mice from the tonic–clonic seizures. The log-probit method was used to calculate the ED50 values. Two ED50 values for CBZ, PB and VPA were statistically analyzed with log-probit method. Three ED50 values for PHT were statistically analyzed with one-way ANOVA and post-hoc Tukey–Kramer test. *P < 0.05 vs.…

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  Fig. 3. Influence of dronedarone (DRO) on total brain concentrations of phenytoin (PHT) in mice. Columns illustrate total brain concentrations (means ± S.E.M.) of PHT (n = 8 mice/column). No significant differences were found between both groups (the unpaired Student’s t test)