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

作者：Sawicka Katarzyna M; Zaluska Katarzyna; Wawryniuk Agnieszka; Zaluska Patel Karolina; Szczyrek Michal; Drop Bartlomiej; Daniluk Jadwiga; Szpringer Monika; Zolkowska Dorota; Luszczki Jarogniew J

来源：Epilepsy Research, 2017, 133: 67-70.

DOI：10.1016/j.eplepsyres.2017.04.011

• Antiepileptic drugs
• Ivabradine
• Maximal electroshock-induced seizures
• Pharmacokinetic/pharmacodynamic interaction

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 < 0.05) in the mouse MES model. In contrast, ivabradine (10 mg/kg, i.p.) did not significantly affect the anticonvulsant potency of lacosamide, pregabalin or topiramate in the mouse MES model. Additionally, ivabradine had no impact on total brain concentrations of all the studied AEDs in mice. A special caution is advised when combining ivabradine with lamotrigine in epilepsy patients due to the possible pharmacodynamic reduction of the anticonvulsant action of the later drug. The combinations of ivabradine with lacosamide, pregabalin and topiramate seem to be pharmacodynamic and neutral from a preclinical viewpoint.

• 出版日期2017-7