Amiodarone Enhances Anticonvulsive Effect of Oxcarbazepine and Pregabalin in the Mouse Maximal Electroshock Model

Accumulating experimental studies show that antiarrhythmic and antiepileptic drugs share some molecular mechanisms of action and can interact with each other. In this study, the influence of amiodarone (a class III antiarrhythmic drug) on the antiseizure action of four second-generation antiepilepti...

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Main Authors: Monika Banach, Monika Rudkowska, Agata Sumara, Kinga Borowicz-Reutt
Format: Article
Language:English
Published: MDPI AG 2021-01-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/3/1041
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author Monika Banach
Monika Rudkowska
Agata Sumara
Kinga Borowicz-Reutt
author_facet Monika Banach
Monika Rudkowska
Agata Sumara
Kinga Borowicz-Reutt
author_sort Monika Banach
collection DOAJ
description Accumulating experimental studies show that antiarrhythmic and antiepileptic drugs share some molecular mechanisms of action and can interact with each other. In this study, the influence of amiodarone (a class III antiarrhythmic drug) on the antiseizure action of four second-generation antiepileptic drugs was evaluated in the maximal electroshock model in mice. Amiodarone, although ineffective in the electroconvulsive threshold test, significantly potentiated the antielectroshock activity of oxcarbazepine and pregabalin. Amiodarone, given alone or in combination with oxcarbazepine, lamotrigine, or topiramate, significantly disturbed long-term memory in the passive-avoidance task in mice. Brain concentrations of antiepileptic drugs were not affected by amiodarone. However, the brain concentration of amiodarone was significantly elevated by oxcarbazepine, topiramate, and pregabalin. Additionally, oxcarbazepine and pregabalin elevated the brain concentration of desethylamiodarone, the main metabolite of amiodarone. In conclusion, potentially beneficial action of amiodarone in epilepsy patients seems to be limited by neurotoxic effects of amiodarone. Although results of this study should still be confirmed in chronic protocols of treatment, special precautions are recommended in clinical conditions. Coadministration of amiodarone, even at low therapeutic doses, with antiepileptic drugs should be carefully monitored to exclude undesired effects related to accumulation of the antiarrhythmic drug and its main metabolite, desethylamiodarone.
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spelling doaj.art-674dbdacc0004320a15ab00e8bfb65942023-12-03T14:09:00ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-01-01223104110.3390/ijms22031041Amiodarone Enhances Anticonvulsive Effect of Oxcarbazepine and Pregabalin in the Mouse Maximal Electroshock ModelMonika Banach0Monika Rudkowska1Agata Sumara2Kinga Borowicz-Reutt3Independent Unit of Experimental Neuropathophysiology, Medical University of Lublin, Jaczewskiego 8b, PL-20-090 Lublin, PolandIndependent Unit of Experimental Neuropathophysiology, Medical University of Lublin, Jaczewskiego 8b, PL-20-090 Lublin, PolandDepartment of Pathophysiology, Medical University of Lublin, Jaczewskiego 8b, PL-20-090 Lublin, PolandIndependent Unit of Experimental Neuropathophysiology, Medical University of Lublin, Jaczewskiego 8b, PL-20-090 Lublin, PolandAccumulating experimental studies show that antiarrhythmic and antiepileptic drugs share some molecular mechanisms of action and can interact with each other. In this study, the influence of amiodarone (a class III antiarrhythmic drug) on the antiseizure action of four second-generation antiepileptic drugs was evaluated in the maximal electroshock model in mice. Amiodarone, although ineffective in the electroconvulsive threshold test, significantly potentiated the antielectroshock activity of oxcarbazepine and pregabalin. Amiodarone, given alone or in combination with oxcarbazepine, lamotrigine, or topiramate, significantly disturbed long-term memory in the passive-avoidance task in mice. Brain concentrations of antiepileptic drugs were not affected by amiodarone. However, the brain concentration of amiodarone was significantly elevated by oxcarbazepine, topiramate, and pregabalin. Additionally, oxcarbazepine and pregabalin elevated the brain concentration of desethylamiodarone, the main metabolite of amiodarone. In conclusion, potentially beneficial action of amiodarone in epilepsy patients seems to be limited by neurotoxic effects of amiodarone. Although results of this study should still be confirmed in chronic protocols of treatment, special precautions are recommended in clinical conditions. Coadministration of amiodarone, even at low therapeutic doses, with antiepileptic drugs should be carefully monitored to exclude undesired effects related to accumulation of the antiarrhythmic drug and its main metabolite, desethylamiodarone.https://www.mdpi.com/1422-0067/22/3/1041amiodaroneantiepileptic drugsdrug interactionsmaximal electroshock-induced seizures
spellingShingle Monika Banach
Monika Rudkowska
Agata Sumara
Kinga Borowicz-Reutt
Amiodarone Enhances Anticonvulsive Effect of Oxcarbazepine and Pregabalin in the Mouse Maximal Electroshock Model
International Journal of Molecular Sciences
amiodarone
antiepileptic drugs
drug interactions
maximal electroshock-induced seizures
title Amiodarone Enhances Anticonvulsive Effect of Oxcarbazepine and Pregabalin in the Mouse Maximal Electroshock Model
title_full Amiodarone Enhances Anticonvulsive Effect of Oxcarbazepine and Pregabalin in the Mouse Maximal Electroshock Model
title_fullStr Amiodarone Enhances Anticonvulsive Effect of Oxcarbazepine and Pregabalin in the Mouse Maximal Electroshock Model
title_full_unstemmed Amiodarone Enhances Anticonvulsive Effect of Oxcarbazepine and Pregabalin in the Mouse Maximal Electroshock Model
title_short Amiodarone Enhances Anticonvulsive Effect of Oxcarbazepine and Pregabalin in the Mouse Maximal Electroshock Model
title_sort amiodarone enhances anticonvulsive effect of oxcarbazepine and pregabalin in the mouse maximal electroshock model
topic amiodarone
antiepileptic drugs
drug interactions
maximal electroshock-induced seizures
url https://www.mdpi.com/1422-0067/22/3/1041
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