Advances in clinical and experimental medicine : official organ Wroclaw Medical University · 2018
Isobolographic additivity among lacosamide, lamotrigine and phenobarbital in a mouse tonic-clonic seizure model.
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Kondrat-Wróbel Maria W, Łuszczki Jarogniew J
Аннотация
BACKGROUND: 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.
OBJECTIVES: 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.
MATERIAL AND METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
OBJECTIVES: 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.
MATERIAL AND METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.