INTERACTION OF THREE-DRUG COMBINATION OF LACOSAMIDE, CARBAMAZEPINE AND PHENOBARBITAL IN THE MOUSE MAXIMAL ELECTROSHOCK-INDUCED SEIZURE MODEL – AN ISOBOLOGRAPHIC ANALYSIS

Background. Epilepsy is one of the serious neurological diseases characterized by seizures that affect about 1% of people worldwide (65 million), and therefore, epilepsy can be considered as a disease of civilization. Although seizures are controllable with antiepileptic drugs (AEDs) in about 70% of cases, it remains still about 30% of epilepsy patients inadequately medicated with these AEDs, who need a full control of their seizure attacks. One of the treatment options in these patients is application of two or three AEDs in combination. The aim of this study was to characterize the anticonvulsant effects of a combination of three AEDs (i.e., carbamazepine [CBZ], lacosamide [LCM] and phenobarbital [PB]) at the fixed-ratio of 1:1:1 in the mouse maximal electroshock (MES)-induced seizure model.

Materials and methods. Tonic hind limb extension (seizure activity) was evoked in adult male albino Swiss mice by a current (sine-wave, 25 mA, 500 V, 50 Hz, 0.2 s stimulus duration) delivered via auricular electrodes. Type I isobolographic analysis was used to analyze the three-drug combination.

Results. Type I isobolographic analysis revealed that the combination of CBZ, LCM and PB (at the fixed-ratio of 1:1:1) exerted additive interaction with a slight tendency towards antagonism in the mouse MES-induced seizure model.

Conclusions. A special caution is advised to patients taking LCM in combination with CBZ and PB because this three-drug combination offered additive interaction with a slight tendency towards antagonism in the mouse MES model.