Title : Dronedarone potentiates the anticonvulsant activity of lamotrigine in the model of tonic-clonic seizures in mice
Abstract:
The purpose of this study was to evaluate the effect of dronedarone (a multi-channel blocker inhibiting outward potassium currents, inward rapid sodium current and L-type calcium channels) on the anticonvulsant properties of some selected antiepileptic drugs (i.e., carbamazepine, lacosamide, lamotrigine and phenytoin) in the mouse maximal electroshockinduced seizure model.
Tonic hindlimb extension (seizure activity) was evoked in adult male albino Swiss mice by a current (25mA, 500V, 50Hz, 0.2s stimulus duration) delivered via ear-clip electrodes.Potential concurrent side effects of interaction between dronedarone and four selected antiepileptic drugs were evaluated in the chimney test (motor performance), passive avoidance task (longterm memory) and grip-strength test (skeletal muscular strength) in mice. Total brain antiepileptic drug concentrations were measured with HPLC to exclude any pharmacokinetic interaction between drugs.
Results provide evidence that dronedarone significantly potentiated the anticonvulsant effects of lamotrigine, but not those of carbamazepine, lacosamide or phenytoin in the maximal electroshock-induced seizure model in mice. No acute adverse effects were associated with the combined treatment of dronedarone with the antiepileptic drugs in the chimney, passive avoidance and grip-strength tests in mice. Pharmacokinetic study revealed that dronedarone did not alter total brain concentrations of lamotrigine in mice, suggesting pharmacodynamic nature of the observed interaction.
In conclusions, significant potentiation of the anticonvulsant effects of lamotrigine by the multi-channel blocker dronedarone in the mouse model of tonic-clonic seizures might suggest that the favorable interaction between drugs could be expected also in humans.
