RESEARCH PAPER
Synergy among oxcarbazepine , pregabalin and topiramate in the mouse maximal electroshockinduced seizure test – an isobolographic analysis
1
Department of Pathophysiology, Medical University, Lublin, Poland
2
Isobolographic Analysis Laboratory, Institute of Rural Health, Lublin, Poland
3
Institute of Rural Health, Isobolographic Analysis Laboratory, Poland
Corresponding author
Jarogniew J. Łuszczki
Medical University of Lublin, Department of Pathophysiology, Department of Pathophysiology, 20-090, Lublin, Poland
Medical University of Lublin, Department of Pathophysiology, Department of Pathophysiology, 20-090, Lublin, Poland
J Pre Clin Clin Res. 2018;12(4):111-116
KEYWORDS
TOPICS
ABSTRACT
Introduction:
Assessment of interactions among antiepileptic drugs (AEDs) during polytherapy is still a challenging issue for physicians and epileptologists worldwide. In spite of 25 currently licensed AEDs, there are no algorithms allowing a proper choice of these drugs to create combinations which would offer epileptic patients an efficacious therapy in the case of seizures refractory to monotherapeutic use of the AEDs. To characterize a type of interaction for a three-drug mixture of oxcarbazepine (OXC), pregabalin (PGB) and topiramate (TPM) in an experimental model of tonic-clonic seizures, an isobolographic analysis of interaction was applied.
Material and methods:
The anticonvulsant effects of the three-drug mixture of OXC, PGB and TPM with respect to suppression of tonic-clonic seizures in mice were assessed in the mouse maximal electroshock-induced seizure model. Type I isobolographic analysis was used to characterize the type of interactions among three AEDs. Potential acute adverse effects were evaluated in the chimney, passive avoidance and grip-strength tests.
Results:
The three-drug mixture of OXC, PGB and TPM exerted supra-additive (synergistic) interaction in the mouse maximal electroshock-induced seizure model. The combination of OXC, PGB and TPM did not produce any acute adverse effects in mice in the chimney, passive avoidance and grip-strength tests.
Conclusions:
The isobolographic synergy observed experimentally for the combination of OXC, PGB and TPM could be recommended to patients with drug-resistant epilepsy, if the results of this study were translated to clinical settings.
Assessment of interactions among antiepileptic drugs (AEDs) during polytherapy is still a challenging issue for physicians and epileptologists worldwide. In spite of 25 currently licensed AEDs, there are no algorithms allowing a proper choice of these drugs to create combinations which would offer epileptic patients an efficacious therapy in the case of seizures refractory to monotherapeutic use of the AEDs. To characterize a type of interaction for a three-drug mixture of oxcarbazepine (OXC), pregabalin (PGB) and topiramate (TPM) in an experimental model of tonic-clonic seizures, an isobolographic analysis of interaction was applied.
Material and methods:
The anticonvulsant effects of the three-drug mixture of OXC, PGB and TPM with respect to suppression of tonic-clonic seizures in mice were assessed in the mouse maximal electroshock-induced seizure model. Type I isobolographic analysis was used to characterize the type of interactions among three AEDs. Potential acute adverse effects were evaluated in the chimney, passive avoidance and grip-strength tests.
Results:
The three-drug mixture of OXC, PGB and TPM exerted supra-additive (synergistic) interaction in the mouse maximal electroshock-induced seizure model. The combination of OXC, PGB and TPM did not produce any acute adverse effects in mice in the chimney, passive avoidance and grip-strength tests.
Conclusions:
The isobolographic synergy observed experimentally for the combination of OXC, PGB and TPM could be recommended to patients with drug-resistant epilepsy, if the results of this study were translated to clinical settings.
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