Epilepsy research · 2022
Electrocorticographic and electrocardiographic evaluation of lacosamide in a penicillin-induced status epilepticus model.
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Sumbul Orhan, Aygun Hatice
Аннотация
AIM: The effect of lacosamide, a new antiseizure medication, was investigated electrophysiologically and biochemically in the penicillin-induced status epilepticus model.
METHOD: The study included seven groups of rats (control, penicillin and 1, 5, 10, 25 and 50 mg/kg lacosamide). The rats were anesthetized using urethane (1.25 mg/kg/i.p.). ECG recordings were taken for one minute before and during status epilepticus in all groups. Lacosamide was administered intraperitoneally 30 min after intracortical microinjection of penicillin (500-IU/2.5/μl) and ECoG recording was taken for 180 min. The brain tissue was evaluated by ELISA method.
RESULTS: Lacosamide (1, 5, 10 and 25 mg/kg) decreased spike frequency significantly, while 50 mg/kg lacosamide dose resulted in an increase in spike frequency. ST segment elevation and heart rate were higher in the penicillin group. Lacosamide doses of 1, 5, 10 and 25 mg/kg decreased ST-segment elevation to the level of the control group, but 50 mg/kg lacosamide increased ST-segment elevation, QT and PR-interval. TOS and TNF-alpha levels increased in the penicillin group compared to control group, while 10 mg/kg lacosamide dose limited this increase. 50 mg/kg lacosamide administration was found to decrease TAS level compared to control group.
CONCLUSION: Our findings indicated associations of the decrease in spike frequency with the reduction of oxidative stress and inflammation in rats treated with 10 mg/kg lacosamide. High doses of lacosamide for acute treatment may cause cardiac changes in ECG.
METHOD: The study included seven groups of rats (control, penicillin and 1, 5, 10, 25 and 50 mg/kg lacosamide). The rats were anesthetized using urethane (1.25 mg/kg/i.p.). ECG recordings were taken for one minute before and during status epilepticus in all groups. Lacosamide was administered intraperitoneally 30 min after intracortical microinjection of penicillin (500-IU/2.5/μl) and ECoG recording was taken for 180 min. The brain tissue was evaluated by ELISA method.
RESULTS: Lacosamide (1, 5, 10 and 25 mg/kg) decreased spike frequency significantly, while 50 mg/kg lacosamide dose resulted in an increase in spike frequency. ST segment elevation and heart rate were higher in the penicillin group. Lacosamide doses of 1, 5, 10 and 25 mg/kg decreased ST-segment elevation to the level of the control group, but 50 mg/kg lacosamide increased ST-segment elevation, QT and PR-interval. TOS and TNF-alpha levels increased in the penicillin group compared to control group, while 10 mg/kg lacosamide dose limited this increase. 50 mg/kg lacosamide administration was found to decrease TAS level compared to control group.
CONCLUSION: Our findings indicated associations of the decrease in spike frequency with the reduction of oxidative stress and inflammation in rats treated with 10 mg/kg lacosamide. High doses of lacosamide for acute treatment may cause cardiac changes in ECG.