Independent Unit of Experimental Neuropathophysiology, Department of Pathophysiology, Medical University of Lublin, Lublin, Poland.
Independent Unit of Experimental Neuropathophysiology, Department of Pathophysiology, Medical University of Lublin, Lublin, Poland.
Pharmacol Rep. 2017 Dec;69(6):1173-1177. doi: 10.1016/j.pharep.2017.05.005. Epub 2017 May 11.
Sotalol as a drug blocking β-receptors and potassium KCNH2 channels may interact with different substances that affect seizures. Herein, we present interactions between sotalol and four conventional antiepileptic drugs: carbamazepine, valproate, phenytoin and phenobarbital.
Effects of sotalol and antiepileptics alone on seizures were determined in the electroconvulsive threshold test, while interactions between sotalol and antiepileptic drugs were estimated in the maximal electroshock test in mice. Motor coordination and long-term memory were evaluated, respectively, in the chimney test and passive-avoidance task. Brain concentrations of antiepileptics were determined by fluorescence polarization immunoassay.
Sotalol at doses up to 100mg/kg did not affect the electroconvulsive threshold. Applied at doses 60-100mg/kg, sotalol potentiated the antielectroshock action of valproate, while at doses 80-100mg/kg that of phenytoin. Sotalol (up to 100mg/kg) did not affect the action of carbamazepine or phenobarbital in the maximal electroshock. Sotalol alone and in combinations with antiepileptics impaired neither motor performance nor long-term memory in mice. Finally, sotalol did not change brain concentration of valproate and phenytoin, so pharmacokinetic interactions between the drugs are not probable.
As far as obtained data may be extrapolated into clinical conditions, sotalol may be considered as an arrhythmic drug that does not reduce the action of classical antiepileptic drugs and thereby can be used in epileptic patients with cardiac arrhythmias.
索他洛尔作为一种阻滞β受体和钾通道 KCNH2 的药物，可能与影响癫痫发作的不同物质相互作用。在此，我们介绍了索他洛尔与四种传统抗癫痫药物：卡马西平、丙戊酸钠、苯妥英和苯巴比妥之间的相互作用。
在电惊厥阈试验中，单独测定索他洛尔和抗癫痫药物对癫痫发作的影响，而在最大电休克试验中，在小鼠中评估索他洛尔和抗癫痫药物之间的相互作用。分别在烟囱试验和被动回避任务中评估运动协调和长期记忆。通过荧光偏振免疫测定法测定抗癫痫药物的脑浓度。
高达 100mg/kg 的索他洛尔剂量不影响电惊厥阈。以 60-100mg/kg 的剂量应用时，索他洛尔增强了丙戊酸钠的抗电休克作用，而以 80-100mg/kg 的剂量增强了苯妥英的抗电休克作用。高达 100mg/kg 的索他洛尔剂量不影响卡马西平和苯巴比妥在最大电休克中的作用。单独使用索他洛尔或与抗癫痫药物联合使用，均不会影响小鼠的运动表现或长期记忆。最后，索他洛尔本身并未改变丙戊酸钠和苯妥英的脑浓度，因此药物之间不太可能存在药代动力学相互作用。
就获得的数据可以推断到临床情况而言，索他洛尔可以被认为是一种抗心律失常药物，它不会降低经典抗癫痫药物的作用，因此可以用于患有心律失常的癫痫患者。
