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Sotalol does not interfere with the antielectroshock action of selected second-generation antiepileptic drugs in mice
BACKGROUND: Due to blocking β-receptors, and potassium KCNH2 channels, sotalol may influence seizure phenomena. In the previous study, we have shown that sotalol potentiated the antielectroshock action of phenytoin and valproate in mice. MATERIALS AND METHODS: As a continuation of previous experimen...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994213/ https://www.ncbi.nlm.nih.gov/pubmed/33492655 http://dx.doi.org/10.1007/s43440-020-00210-2 |
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author | Borowicz-Reutt, Kinga K. Banach, Monika Rudkowska, Monika Stachniuk, Anna |
author_facet | Borowicz-Reutt, Kinga K. Banach, Monika Rudkowska, Monika Stachniuk, Anna |
author_sort | Borowicz-Reutt, Kinga K. |
collection | PubMed |
description | BACKGROUND: Due to blocking β-receptors, and potassium KCNH2 channels, sotalol may influence seizure phenomena. In the previous study, we have shown that sotalol potentiated the antielectroshock action of phenytoin and valproate in mice. MATERIALS AND METHODS: As a continuation of previous experiments, we examined the effect of sotalol on the action of four chosen second-generation antiepileptic drugs (oxcarbazepine, lamotrigine, pregabalin, and topiramate) against the maximal electroshock in mice. Undesired effects were evaluated in the chimney test (motor impairment) and step-through passive-avoidance task (long-term memory deficits). Finally, brain concentrations of antiepileptics were determined by fluorescence polarization immunoassay, while those of sotalol by liquid chromatography–mass spectrometry. RESULTS: Sotalol at doses of up to 100 mg/kg did not affect the electroconvulsive threshold. Applied at doses of 80–100 mg/kg, sotalol did not affect the antielectroshock action of oxcarbazepine, lamotrigine, pregabalin, or topiramate. Sotalol alone and in combinations with antiepileptics impaired neither motor performance nor long-term memory. Finally, sotalol significantly decreased the brain concentrations of lamotrigine and increased those of oxcarbazepine and topiramate. Pharmacokinetic interactions, however, did not influence the final antielectroshock effects of above-mentioned drug combinations. On the other hand, the brain concentrations of sotalol were not changed by second-generation antiepileptics used in this study. CONCLUSION: Sotalol did not reduce the antielectroshock action of four second-generation antiepileptic drugs examined in this study. Therefore, this antidepressant drug should not interfere with antiseizure effects of lamotrigine, oxcarbazepine, pregabalin, and topiramate in patients with epilepsy. To draw final conclusions, our preclinical data should still be confirmed in other experimental models and clinical conditions. |
format | Online Article Text |
id | pubmed-7994213 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-79942132021-04-16 Sotalol does not interfere with the antielectroshock action of selected second-generation antiepileptic drugs in mice Borowicz-Reutt, Kinga K. Banach, Monika Rudkowska, Monika Stachniuk, Anna Pharmacol Rep Article BACKGROUND: Due to blocking β-receptors, and potassium KCNH2 channels, sotalol may influence seizure phenomena. In the previous study, we have shown that sotalol potentiated the antielectroshock action of phenytoin and valproate in mice. MATERIALS AND METHODS: As a continuation of previous experiments, we examined the effect of sotalol on the action of four chosen second-generation antiepileptic drugs (oxcarbazepine, lamotrigine, pregabalin, and topiramate) against the maximal electroshock in mice. Undesired effects were evaluated in the chimney test (motor impairment) and step-through passive-avoidance task (long-term memory deficits). Finally, brain concentrations of antiepileptics were determined by fluorescence polarization immunoassay, while those of sotalol by liquid chromatography–mass spectrometry. RESULTS: Sotalol at doses of up to 100 mg/kg did not affect the electroconvulsive threshold. Applied at doses of 80–100 mg/kg, sotalol did not affect the antielectroshock action of oxcarbazepine, lamotrigine, pregabalin, or topiramate. Sotalol alone and in combinations with antiepileptics impaired neither motor performance nor long-term memory. Finally, sotalol significantly decreased the brain concentrations of lamotrigine and increased those of oxcarbazepine and topiramate. Pharmacokinetic interactions, however, did not influence the final antielectroshock effects of above-mentioned drug combinations. On the other hand, the brain concentrations of sotalol were not changed by second-generation antiepileptics used in this study. CONCLUSION: Sotalol did not reduce the antielectroshock action of four second-generation antiepileptic drugs examined in this study. Therefore, this antidepressant drug should not interfere with antiseizure effects of lamotrigine, oxcarbazepine, pregabalin, and topiramate in patients with epilepsy. To draw final conclusions, our preclinical data should still be confirmed in other experimental models and clinical conditions. Springer International Publishing 2021-01-25 2021 /pmc/articles/PMC7994213/ /pubmed/33492655 http://dx.doi.org/10.1007/s43440-020-00210-2 Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Borowicz-Reutt, Kinga K. Banach, Monika Rudkowska, Monika Stachniuk, Anna Sotalol does not interfere with the antielectroshock action of selected second-generation antiepileptic drugs in mice |
title | Sotalol does not interfere with the antielectroshock action of selected second-generation antiepileptic drugs in mice |
title_full | Sotalol does not interfere with the antielectroshock action of selected second-generation antiepileptic drugs in mice |
title_fullStr | Sotalol does not interfere with the antielectroshock action of selected second-generation antiepileptic drugs in mice |
title_full_unstemmed | Sotalol does not interfere with the antielectroshock action of selected second-generation antiepileptic drugs in mice |
title_short | Sotalol does not interfere with the antielectroshock action of selected second-generation antiepileptic drugs in mice |
title_sort | sotalol does not interfere with the antielectroshock action of selected second-generation antiepileptic drugs in mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994213/ https://www.ncbi.nlm.nih.gov/pubmed/33492655 http://dx.doi.org/10.1007/s43440-020-00210-2 |
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