Tehreem Saba, Sabir Azka, Farooq Maryam, Ashraf Waseem, Alqahtani Faleh, Ahmad Tanveer, Imran Imran
Department of Pharmacology, Faculty of Pharmacy, Bahauddin Zakariya University, Multan, Pakistan.
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Animal Model Exp Med. 2025 Feb;8(2):222-238. doi: 10.1002/ame2.12524. Epub 2025 Jan 23.
Scientific evidence to guide clinicians on the use of different antiseizure drugs in combination therapy is either very limited or lacking. In this study, the impact of lacosamide and perampanel alone and in combination was tested in corneal kindling model in mice, which is a cost-effective mechanism for screening of antiseizure drugs.
The impact of lacosamide (5 mg/kg) and perampanel (0.125 mg/kg) alone and their combination was tested in corneal kindling process (3-mA current for 3 s applied twice daily for consecutive 12 days) in male BALB/c mice. Post-kindling, mice were subjected to a battery of behavioral tests assessing anxiety, memory, and depression-like behaviors. Brain tissues were then harvested for analysis of oxidative stress biomarkers.
Our results showed that the combination therapy of lacosamide and perampanel was more effective in reducing seizure progression than monotherapy of these drugs. Animals treated with combination therapy showed significant behavioral improvements, as reduced anxiety and depression were noticed, and their cognitive abilities were notably better compared to animals of all other groups. Moreover, biochemical assays of isolated brains from combination-treated group revealed lesser amount of oxidative stress. In addition, outcomes of dual regime were comparable to the phenytoin in seizure control but showed superior benefits in mitigation of kindling-prompted behavioral dysfunction and oxidative stress.
This study suggests that the lacosamide and perampanel combination therapy worked noticeably better in halting the corneal kindling process in mice and improved the epilepsy-associated psychiatric disorders that might be due to antioxidant effects of both drugs.
指导临床医生在联合治疗中使用不同抗癫痫药物的科学证据非常有限或缺乏。在本研究中，在小鼠角膜点燃模型中测试了拉科酰胺和吡仑帕奈单独及联合使用的效果，该模型是一种筛选抗癫痫药物的经济有效机制。
在雄性BALB/c小鼠的角膜点燃过程（连续12天每天两次施加3 mA电流持续3秒）中测试拉科酰胺（5 mg/kg）和吡仑帕奈（0.125 mg/kg）单独及联合使用的效果。点燃后，对小鼠进行一系列行为测试，评估焦虑、记忆和抑郁样行为。然后采集脑组织分析氧化应激生物标志物。
我们的结果表明，拉科酰胺和吡仑帕奈联合治疗在减少癫痫发作进展方面比这些药物的单一疗法更有效。接受联合治疗的动物表现出显著的行为改善，焦虑和抑郁减轻，与所有其他组的动物相比，它们的认知能力明显更好。此外，联合治疗组分离脑的生化分析显示氧化应激量较少。此外，双重治疗方案在癫痫控制方面的结果与苯妥英相当，但在减轻点燃引起的行为功能障碍和氧化应激方面显示出更好的效果。
本研究表明，拉科酰胺和吡仑帕奈联合治疗在阻止小鼠角膜点燃过程中效果显著更好，并改善了可能由于两种药物的抗氧化作用导致的癫痫相关精神障碍。
