Ivabradine attenuates the anticonvulsant potency of lamotrigine, but not that of lacosamide, pregabalin and topiramate in the tonic-clonic seizure model in mice

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are involved not only in synaptic transmission and neuronal excitability under physiological conditions, but also in seizure activity. To determine the influence of ivabradine (an HCN channel inhibitor) on the anticonvulsant potency of four novel antiepileptic drugs (AEDs: lacosamide, lamotrigine, pregabalin and topiramate) in the mouse maximal electroshock-induced seizure (MES) model. Adult male albino Swiss mice were challenged with maximal electroconvulsions (electric current of 25 mA delivered via auricular electrodes). Total brain concentrations of AEDs were measured with high-pressure liquid chromatography. Ivabradine (10 mg/kg, i.p.) significantly reduced the anticonvulsant potency of lamotrigine by elevating the ED50 value of the AED from 7.48 (6.15–9.11) to 10.07 (8.85–11.45) mg/kg (P