Dronedarone (a multichannel blocker) enhances the anticonvulsant potency of lamotrigine, but not that of lacosamide, pregabalin and topiramate in the tonic-clonic seizure model in mice

Sawicka, Katarzyna; Florek-Łuszczki, Magdalena; Wawryniuk, Agnieszka; Daniluk, Jadwiga; Wróblewska-Łuczka, Paula; Chmielewski, Jarosław; Karwan, Sławomir; Łuszczki, Jarogniew J.

doi:10.1016/j.eplepsyres.2019.04.007

Cited by 7 publications

(5 citation statements)

References 39 publications

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“…Surprisingly, dronedarone diminished the effect of phenytoin in the MES test in mice. The two pure multichannel blockers did not produce any pharmacokinetic interactions [ 32 , 33 , 34 , 35 ]. Surprisingly, amiodarone and dronedarone, although structurally related to each other, enhanced the action of different antiepileptic drugs.…”

Section: Discussionmentioning

confidence: 99%

“…Dronedarone (50 mg/kg) significantly enhanced the anticonvulsant potency of lamotrigine but did not affect the anticonvulsant properties of lacosamide, pregabalin, or topiramate in the MES test in mice. The measurement of total brain concentrations of phenytoin and lamotrigine revealed that dronedarone did not significantly alter total brain concentrations of lamotrigine in experimental animals, so interactions observed between dronedarone and the two antiepileptics seem to be pharmacodynamic in nature [ 35 ].…”

Section: Antiarrhythmic Drugs Have Different Effects On Tonic–clonic ...mentioning

confidence: 99%

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Effects of Antiarrhythmic Drugs on Antiepileptic Drug Action—A Critical Review of Experimental Findings

Borowicz-Reutt

2022

IJMS

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Severe cardiac arrhythmias developing in the course of seizures increase the risk of SUDEP (sudden unexpected death in epilepsy). Hence, epilepsy patients with pre-existing arrhythmias should receive appropriate pharmacotherapy. Concomitant treatment with antiarrhythmic and antiseizure medications creates, however, the possibility of drug–drug interactions. This is due, among other reasons, to a similar mechanism of action. Both groups of drugs inhibit the conduction of electrical impulses in excitable tissues. The aim of this review was the analysis of such interactions in animal seizure models, including the maximal electroshock (MES) test in mice, a widely accepted screening test for antiepileptic drugs.

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Section: Discussionmentioning

confidence: 99%

Section: Antiarrhythmic Drugs Have Different Effects On Tonic–clonic ...mentioning

confidence: 99%

Effects of Antiarrhythmic Drugs on Antiepileptic Drug Action—A Critical Review of Experimental Findings

Borowicz-Reutt

2022

IJMS

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“…All the studied drugs, except for valproate (i.e., borneol, scoparone, carbamazepine, phenobarbital and phenytoin), were suspended in a 1% aqueous solution of Tween 80 (Sigma-Aldrich, Poznań, Poland), while valproate was dissolved in distilled water. The ASMs were administered intraperitoneally ( ip ) as follows: phenytoin—120 min, phenobarbital—60 min and carbamazepine and valproate—30 min, before the experiments, as reported earlier [ 39 , 40 ]. Borneol and scoparone were injected i.p.…”

Section: Methodsmentioning

confidence: 99%

Antiseizure Effects of Scoparone, Borneol and Their Impact on the Anticonvulsant Potency of Four Classic Antiseizure Medications in the Mouse MES Model—An Isobolographic Transformation

Łuszczki

Bojar

Góralczyk

et al. 2023

IJMS

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Numerous botanical drugs containing coumarins and terpenes are used in ethnomedicine all over the world for their various therapeutic properties, especially those affecting the CNS system. The treatment of epilepsy is based on antiseizure medications (ASMs), although novel strategies using naturally occurring substances with confirmed antiseizure properties are being developed nowadays. The aim of this study was to determine the anticonvulsant profiles of scoparone (a simple coumarin) and borneol (a bicyclic monoterpenoid) when administered separately and in combination, as well as their impact on the antiseizure effects of four classic ASMs (carbamazepine, phenytoin, phenobarbital and valproate) in the mouse model of maximal electroshock-induced (MES) tonic-clonic seizures. MES-induced seizures were evoked in mice receiving the respective doses of the tested natural compounds and classic ASMs (when applied alone or in combinations). Interactions for two-drug and three-drug mixtures were assessed by means of isobolographic transformation of data. Polygonograms were used to illustrate the types of interactions occurring among drugs. The total brain content of ASMs was measured in mice receiving the respective drug treatments with fluorescent polarization immunoassay. Scoparone and borneol, when administered alone, exerted anticonvulsant properties in the mouse MES model. The two-drug mixtures of scoparone with valproate, borneol with phenobarbital and borneol with valproate produced synergistic interactions in the mouse MES model, while the remaining tested two-drug mixtures produced additivity. The three-drug mixtures of scoparone + borneol with valproate and phenobarbital produced synergistic interactions in the mouse MES model. Verification of total brain concentrations of valproate and phenobarbital revealed that borneol elevated the total brain concentrations of both ASMs, while scoparone did not affect the brain content of these ASMs in mice. The synergistic interaction of scoparone with valproate observed in the mouse MES model is pharmacodynamic in nature. Borneol elevated the brain concentrations of the tested ASMs, contributing to the pharmacokinetic nature of the observed synergistic interactions with valproate and phenobarbital in the mouse MES model.

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“…Clinical evidence shows that the combination of dronedarone with lacosamide should be neutral from a clinical viewpoint, and a special attention is recommended for patients with GTCS because of some adverse-effects. 131 In a clinical study, Abarrategui et al assessed the effect of lacosamide on refractory epilepsy and suggested that lacosamide can be a reasonable option for patients with this type of epilepsy. 132…”

Section: Lacosamidementioning

confidence: 99%

Experimental Therapeutic Strategies in Epilepsies Using Anti-Seizure Medications

Rahim¹,

Azizimalamiri²,

Sayyah³

et al. 2021

JEP

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Epilepsies are among the most common neurological problems. The disease burden in patients with epilepsy is significantly high, and epilepsy has a huge negative impact on patients’ quality of life with epilepsy and their families. Anti-seizure medications are the mainstay treatment in patients with epilepsy, and around 70% of patients will ultimately control with a combination of at least two appropriately selected anti-seizure medications. However, in one-third of patients, seizures are resistant to drugs, and other measures will be needed. The primary goal in using experimental therapeutic medication strategies in patients with epilepsy is to prevent recurrent seizures and reduce the rate of traumatic events that may occur during seizures. So far, various treatments using medications have been offered for patients with epilepsies, which have been classified according to the type of epilepsy, the effectiveness of the medications, and the adverse effects. Medications such as Levetiracetam, valproic acid, and lamotrigine are at the forefront of these patients’ treatment. Epilepsy surgery, neuro-stimulation, and the ketogenic diet are the main measures in patients with medication-resistant epilepsies. In this paper, we will review the therapeutic approach using anti-seizure medications in patients with epilepsy. However, it should be noted that some of these patients still do not respond to existing treatments; therefore, the limited ability of current therapies has fueled research efforts for the development of novel treatment strategies. Thus, it seems that in addition to surgical measures, we should look for more specific agents that have less adverse events and have a greater effect in stopping seizures.

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Dronedarone (a multichannel blocker) enhances the anticonvulsant potency of lamotrigine, but not that of lacosamide, pregabalin and topiramate in the tonic-clonic seizure model in mice

Cited by 7 publications

References 39 publications

Effects of Antiarrhythmic Drugs on Antiepileptic Drug Action—A Critical Review of Experimental Findings

Effects of Antiarrhythmic Drugs on Antiepileptic Drug Action—A Critical Review of Experimental Findings

Antiseizure Effects of Scoparone, Borneol and Their Impact on the Anticonvulsant Potency of Four Classic Antiseizure Medications in the Mouse MES Model—An Isobolographic Transformation

Experimental Therapeutic Strategies in Epilepsies Using Anti-Seizure Medications

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