Department of Internal Medicine in Nursing, Medical University of Lublin, Lublin, Poland; Department of Pathophysiology, Medical University of Lublin, Lublin, Poland.
Department of Medical Anthropology, Institute of Rural Health, Lublin, Poland.
Epilepsy Res. 2019 Aug;154:62-68. doi: 10.1016/j.eplepsyres.2019.04.007. Epub 2019 Apr 22.
Accumulating experimental evidence indicates that some recently licensed antiarrhythmic drugs, including dronedarone (a multichannel blocker) play a crucial role in initiation of seizures in both, in vivo and in vitro studies. Some of these antiarrhythmic drugs elevate the threshold for maximal electroconvulsions and enhance the anticonvulsant potency of classical antiepileptic drugs in preclinical studies. This study was aimed at determining the influence of dronedarone (an antiarrhythmic drug) on the anticonvulsant potency of four novel antiepileptic drugs (lacosamide, lamotrigine, pregabalin and topiramate) in the maximal electroshock-induced seizure model in mice. To exclude any potential pharmacokinetic contribution of dronedarone to the observed interactions, total brain concentrations of antiepileptic drugs were measured. Dronedarone (50 mg/kg, i.p.) significantly enhanced the anticonvulsant potency of lamotrigine, by reducing its ED value from 7.67 mg/kg to 4.19 mg/kg (P < 0.05), in the maximal electroshock-induced seizure test in mice. On the contrary, dronedarone (50 mg/kg, i.p.) did not affect the anticonvulsant properties of lacosamide, pregabalin or topiramate in the maximal electroshock-induced seizure test in mice. Measurement of total brain concentrations of lamotrigine revealed that dronedarone did not significantly alter total brain concentrations of lamotrigine in experimental animals. Additionally, the combination of dronedarone with pregabalin significantly impaired motor coordination in animals subjected to the chimney test. In contrast, the combinations of other studied antiepileptic drugs with dronedarone had no negative influence on motor coordination in mice. It is advisable to combine dronedarone with lamotrigine to enhance the anticonvulsant potency of the latter drug. The combinations of dronedarone with lacosamide, pregabalin and topiramate resulted in neutral interactions in the maximal electroshock-induced seizure test in mice. However, a special caution is advised to patients receiving both, pregabalin and dronedarone due to some possible adverse effects that might occur with respect to motor coordination.
越来越多的实验证据表明，一些最近获得许可的抗心律失常药物，包括决奈达隆（多通道阻滞剂），在体内和体外研究中都在癫痫发作的启动中起着至关重要的作用。这些抗心律失常药物中的一些会提高最大电惊厥的阈值，并在临床前研究中增强经典抗癫痫药物的抗惊厥作用。本研究旨在确定决奈达隆（一种抗心律失常药物）对四种新型抗癫痫药物（拉科酰胺、拉莫三嗪、普瑞巴林和托吡酯）在最大电休克诱导的惊厥模型中的抗惊厥作用的影响。为了排除决奈达隆对观察到的相互作用的任何潜在药代动力学贡献，测量了抗癫痫药物的总脑浓度。决奈达隆（50mg/kg，ip）显著增强了拉莫三嗪的抗惊厥作用，将其 ED 值从 7.67mg/kg 降低至 4.19mg/kg（P<0.05），在最大电休克诱导的惊厥试验中。相反，决奈达隆（50mg/kg，ip）对拉科酰胺、普瑞巴林或托吡酯在最大电休克诱导的惊厥试验中的抗惊厥特性没有影响。拉莫三嗪总脑浓度的测量表明，决奈达隆并没有显著改变实验动物中拉莫三嗪的总脑浓度。此外，在进行烟囱试验的动物中，决奈达隆与普瑞巴林的联合使用显著损害了运动协调能力。相比之下，与其他研究的抗癫痫药物与决奈达隆的组合对小鼠的运动协调没有负面影响。将决奈达隆与拉莫三嗪联合使用以增强后者的抗惊厥作用是明智的。在最大电休克诱导的惊厥试验中，决奈达隆与拉科酰胺、普瑞巴林和托吡酯的组合结果呈中性相互作用。然而，鉴于可能发生与运动协调相关的一些不良影响，建议接受普瑞巴林和决奈达隆治疗的患者谨慎使用。
