eISSN: 2354-0265
ISSN: 2353-6942
Health Problems of Civilization Physical activity: diseases and issues recognized by the WHO
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1/2019
vol. 13
 
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abstract:
Original paper

Antagonistic interaction of lacosamide with carbamazepine and valproate in the mouse tonic-clonic seizure model

Maria W. Kondrat-Wróbel
1
,
Katarzyna Załuska
1
,
Aleksandra Walczak
1
,
Anna N. Panasiuk-Poterek
1
,
Agata Gut-Lepiech
1
,
Paula Wróblewska-Łuczka
1
,
Jarogniew J. Łuszczki
1, 2

  1. Department of Pathophysiology, Medical University of Lublin, Poland
  2. Isobolographic Analysis Laboratory, Institute of Rural Health, Lublin, Poland
Health Prob Civil. 2019; 13(1): 92-98
DOI: https://doi.org/10.5114/hpc.2019.81105
Online publish date: 2019/01/30
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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.

keywords:

antiepileptic drugs, isobolography, maximal electroshock, three-drug combination, antagonism

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