Interactions of pregabalin with gabapentin, levetiracetam, tiagabine and vigabatrin in the mouse maximal electroshock-induced seizure model: A type II isobolographic analysis

Łuszczki, Jarogniew J.; Filip, Damian; Florek-Łuszczki, Magdalena

doi:10.1016/j.eplepsyres.2011.09.002

Cited by 12 publications

(10 citation statements)

References 51 publications

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“…Our results presented in this study are generally consistent with those documenting earlier synergistic interactions between levetiracetam and carbamazepine, oxcarbazepine, felbamate, topiramate in the mouse MES model [20,21] . In contrast, the combinations of levetiracetam with phenytoin, phenobarbital, valproate, lamotrigine, pregabalin and 1-methyl-1,2,3,4-tetrahydroisoquinoline were additive in the mouse MES model [10,20,22] . Moreover, it has been found that retigabine combined with valproate produced synergistic interactions [11] , while the combination of retigabine with carbamazepine, oxcarbazepine, lamotrigine, phenytoin, lacosamide and topiramate exerted additive interactions in the mouse MES model [11,16] .…”

Section: Discussionmentioning

confidence: 99%

Synergistic Interaction of Retigabine with Levetiracetam in the Mouse Maximal Electroshock-Induced Seizure Model: A Type II Isobolographic Analysis

Łuszczki

Zagaja²,

Miziak³

et al. 2015

Pharmacology

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Background/Aims: To assess interactions between retigabine and levetiracetam in suppressing maximal electroshock-induced tonic seizures in Albino Swiss mice, type II isobolographic analysis was used. Total brain antiepileptic drug concentrations were measured with high pressure liquid chromatography. Results: The combinations of retigabine with levetiracetam at the fixed-ratios of 1:5 and 1:10 were supra-additive (synergistic; p < 0.05) in terms of seizure suppression, while the combinations at the fixed-ratios of 1:1 and 1:2 were additive. No pharmacokinetic changes in total brain concentrations of levetiracetam and retigabine were documented, indicating the pharmacodynamic nature of interaction between these antiepileptic drugs in the mouse maximal electroshock-induced tonic seizure model. Conclusion: The combination of retigabine with levetiracetam at the fixed-ratios of 1:5 and 1:10 appears to be particularly beneficial combination exerting supra-additive interaction in suppressing maximal electroshock-induced tonic seizures.

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Section: Discussionmentioning

confidence: 99%

Synergistic Interaction of Retigabine with Levetiracetam in the Mouse Maximal Electroshock-Induced Seizure Model: A Type II Isobolographic Analysis

Łuszczki

Zagaja²,

Miziak³

et al. 2015

Pharmacology

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“…The clinical usage of second-and third-generation antiepileptic drugs is usually associated with low risk of adverse effects evoked by these antiepileptic drugs in epileptic patients [21]. Unfortunately, favorable combinations of antiepileptic drugs exclusively comprised the second-and third-generation antiepileptic drugs are scarce [22][23][24][25][26][27][28]. To ensure the patients with refractory epilepsy with the best treatment options, experiments on animals should verify, which of the tested antiepileptic drug combinations are beneficial and exert synergistic interactions with respect to their anticonvulsant effects that would be transferred to clinical conditions.…”

Section: Introductionmentioning

confidence: 99%

Polygonogram and isobolographic analysis of interactions between various novel antiepileptic drugs in the 6-Hz corneal stimulation-induced seizure model in mice

et al. 2020

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Pharmacotherapy with two antiepileptic drugs in combination is usually prescribed to epilepsy patients with refractory seizures. The choice of antiepileptic drugs in combination should be based on synergistic cooperation of the drugs with respect to suppression of seizures. The selection of synergistic interactions between antiepileptic drugs is challenging issue for physicians, especially, if 25 antiepileptic drugs are currently available and approved to treat epilepsy patients. The aim of this study was to determine all possible interactions among 5 second-generation antiepileptic drugs (gabapentin (GBP), lacosamide (LCM), levetiracetam (LEV), pregabalin (PGB) and retigabine (RTG)) in the 6-Hz corneal stimulation-induced seizure model in adult male albino Swiss mice. The anticonvulsant effects of 10 various two-drug combinations of antiepileptic drugs were evaluated with type I isobolographic analysis associated with graphical presentation of polygonogram to visualize the types of interactions. Isobolographic analysis revealed that 7 two-drug combinations of LEV+RTG, LEV+LCM, GBP+RTG, PGB+LEV, GBP+LEV, PGB+RTG, PGB+LCM were synergistic in the 6-Hz corneal stimulation-induced seizure model in mice. The additive interaction was observed for the combinations of GBP+LCM, GBP+PGB, and RTG+LCM in this seizure model in mice. The most beneficial combination, offering the highest level of synergistic suppression of seizures in mice was that of LEV+RTG, whereas the most additive combination that protected the animals from seizures was that reporting additivity for RTG +LCM. The strength of interaction for two-drug combinations can be arranged from the synergistic to the additive, as follows: LEV+RTG > LEV+LCM > GBP+RTG > PGB+LEV > GBP +LEV > PGB+RTG > PGB+LCM > GBP+LCM > GBP+PGB > RTG+LCM.

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“…The mice protected from tonic-clonic seizures out of eight animals in each experimental group allowed to construct doseresponse effect line, according to the log-probit method [21]. The anticonvulsant effects of CBZ, PB and VPA (when administered separately and in the three-drug mixture at the fixed-ratio of 1:1:1) were expressed as the median effective doses (ED 50 in mg/kg) for the AEDs administered separately and the experimental median effective dose (ED 50 exp in mg/ kg) for the three-drug mixture, as presented elsewhere [7,15,[22][23][24][25].…”

Section: Methodsmentioning

confidence: 99%

Additive suppression of tonic-clonic seizures in mice receiving the combination of carbamazepine, phenobarbital and valproate

Załuska¹,

Marzęda²,

Bojar³

et al. 2019

J Pre Clin Clin Res.

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Introduction. Polytherapy with three antiepileptic drugs (AEDs) is used in patients who have seizure episodes classified by physicians and neurologists as refractory or drug-resistant. Although doctors can prescribe these patients 25 various AEDs, no algorithms are available which allow them to choose the most efficacious combinations of AED. Objective. The aim of this study was to isobolographically classify interaction among three classical AEDs (carbamazepine, phenobarbital and valproate), applied in the fixed-ratio combination of 1:1:1, in the maximal electroshock-induced seizures in mice. Materials and method. The anti-seizure activity of the mixture of carbamazepine, phenobarbital and valproate (in the fixed-ratio of 1:1:1) was determined in maximal electroshock-induced seizures-an experimental model of tonic-clonic seizures in mice using type I isobolographic analysis. Results. The mixture of carbamazepine, phenobarbital and valproate (in the fixed-ratio of 1:1:1) produced additive interaction in the maximal electroshock-induced seizure model in mice. The experimentally-derived median effective dose (ED50 exp value) for the mixture was 94.35 mg/kg, whereas the theoretically additive median effective dose (ED50 add value) amounted to 116.77 mg/kg. Conclusions. Although the combination of carbamazepine, phenobarbital and valproate exerted additivity in the mouse maximal electroshock-induced seizure model, it could be recommended for the treatment of patients, if the results of this study would be directly transposed to clinical settings.

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Interactions of pregabalin with gabapentin, levetiracetam, tiagabine and vigabatrin in the mouse maximal electroshock-induced seizure model: A type II isobolographic analysis

Cited by 12 publications

References 51 publications

Synergistic Interaction of Retigabine with Levetiracetam in the Mouse Maximal Electroshock-Induced Seizure Model: A Type II Isobolographic Analysis

Synergistic Interaction of Retigabine with Levetiracetam in the Mouse Maximal Electroshock-Induced Seizure Model: A Type II Isobolographic Analysis

Polygonogram and isobolographic analysis of interactions between various novel antiepileptic drugs in the 6-Hz corneal stimulation-induced seizure model in mice

Additive suppression of tonic-clonic seizures in mice receiving the combination of carbamazepine, phenobarbital and valproate

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