Kondrat-Wróbel Maria W, Łuszczki Jarogniew J
Department of Pathophysiology, Medical University of Lublin, Poland.
Isobolographic Analysis Laboratory, Institute of Rural Health, Lublin, Poland.
Adv Clin Exp Med. 2018 Jul;27(7):881-886. doi: 10.17219/acem/69132.
Epilepsy is a serious neurological disease affecting about 1% of people worldwide (65 million). Seizures are controllable with antiepileptic drugs (AEDs) in about 70% of epilepsy patients, however, there remains about 30% of patients inadequately medicated with these AEDs, who need a satisfactory control of their seizure attacks. For these patients, one of the treatment options is administration of 2 or 3 AEDs in combination.
To determine the anticonvulsant effects of a combination of 3 selected AEDs (i.e., lacosamide - LCM, lamotrigine - LTG and phenobarbital - PB) at the fixed-ratio of 1:1:1 in a mouse maximal electroshock-induced (tonic-clonic) seizure model by using isobolographic analysis.
Seizure activity was evoked in adult male albino Swiss mice by a current (sinewave, 25 mA, 500 V, 50 Hz, 0.2 s stimulus duration) delivered via auricular electrodes. Type I isobolographic analysis was used to detect interaction for the 3-drug combination.
With type I isobolographic analysis, the combination of LCM, LTG and PB (at the fixed-ratio of 1:1:1) exerted additive interaction in the mouse maximal electroshock-induced (tonic-clonic) seizure model.
The combination of LCM with LTG and PB produced additive interaction in the mouse tonicclonic seizure model, despite various molecular mechanisms of action of the tested AEDs.
癫痫是一种严重的神经系统疾病，全球约1%的人口（6500万）受其影响。约70%的癫痫患者可通过抗癫痫药物（AEDs）控制癫痫发作，然而，仍有30%的患者使用这些AEDs治疗效果不佳，需要对癫痫发作进行满意控制。对于这些患者，治疗选择之一是联合使用2种或3种AEDs。
通过等效应线图分析，确定在小鼠最大电休克诱导（强直-阵挛性）癫痫模型中，3种选定的AEDs（即拉科酰胺-LCM、拉莫三嗪-LTG和苯巴比妥-PB）以1:1:1固定比例联合使用时的抗惊厥作用。
通过耳电极施加电流（正弦波，25 mA，500 V，50 Hz，刺激持续时间0.2 s）诱发成年雄性白化瑞士小鼠的癫痫活动。使用I型等效应线图分析检测3种药物联合使用时的相互作用。
通过I型等效应线图分析，LCM、LTG和PB（以1:1:1固定比例）联合使用在小鼠最大电休克诱导（强直-阵挛性）癫痫模型中表现为相加作用。
尽管所测试的AEDs作用机制各不相同，但LCM与LTG和PB联合使用在小鼠强直阵挛性癫痫模型中产生了相加作用。
