OTHER / RESEARCH PAPER
Antagonistic interaction of lacosamide with carbamazepine and valproate in the mouse tonic-clonic seizure model
1
Department of Pathophysiology, Medical University of Lublin, Poland
2
Isobolographic Analysis Laboratory, Institute of Rural Health, Lublin, Poland
Submission date: 2018-08-07
Acceptance date: 2018-10-17
Publication date: 2019-01-30
Health Prob Civil. 2019;13(1):92-98
KEYWORDS
TOPICS
ABSTRACT
Background:
It is estimated that approximately 1% of people worldwide suffer from epilepsy. Currently available antiepileptic drugs (AEDs) are able to control epileptic seizures in about 70% of cases. In the remaining patients (30%), the application of two or three AEDs in combination is necessary for effective seizure management. The goal of this work was to characterize the interaction of three AEDs: lacosamide (LCM), carbamazepine (CBZ) and valproate (VPA) at the fixed-ratio of 1:1:1 in the mouse tonic-clonic seizure model.
Material and methods:
Male albino Swiss mice, after receiving a combination of LCM, CBZ and VPA, were challenged with electric current to evoke tonic hind limb extension (seizure activity). Protection of the mice from tonic-clonic seizures was assessed by isobolographic analysis to determine the type of interaction occurring between these drugs.
Results:
Type I isobolographic analysis revealed that the combination of LCM, CBZ and VPA produced infra-additive (antagonistic) interaction in the mouse tonic-clonic seizure model.
Conclusions:
Since the three-drug mixture of LCM, CBZ and VPA exerted an antagonistic interaction in the tonic-clonic seizure test in mice, we would caution physicians against treating epilepsy patients with this unfavorable combination.
It is estimated that approximately 1% of people worldwide suffer from epilepsy. Currently available antiepileptic drugs (AEDs) are able to control epileptic seizures in about 70% of cases. In the remaining patients (30%), the application of two or three AEDs in combination is necessary for effective seizure management. The goal of this work was to characterize the interaction of three AEDs: lacosamide (LCM), carbamazepine (CBZ) and valproate (VPA) at the fixed-ratio of 1:1:1 in the mouse tonic-clonic seizure model.
Material and methods:
Male albino Swiss mice, after receiving a combination of LCM, CBZ and VPA, were challenged with electric current to evoke tonic hind limb extension (seizure activity). Protection of the mice from tonic-clonic seizures was assessed by isobolographic analysis to determine the type of interaction occurring between these drugs.
Results:
Type I isobolographic analysis revealed that the combination of LCM, CBZ and VPA produced infra-additive (antagonistic) interaction in the mouse tonic-clonic seizure model.
Conclusions:
Since the three-drug mixture of LCM, CBZ and VPA exerted an antagonistic interaction in the tonic-clonic seizure test in mice, we would caution physicians against treating epilepsy patients with this unfavorable combination.
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