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Sotalol does not interfere with the antielectroshock action of selected second-generation antiepileptic drugs in mice.
- Source :
-
Pharmacological reports : PR [Pharmacol Rep] 2021 Apr; Vol. 73 (2), pp. 516-524. Date of Electronic Publication: 2021 Jan 25. - Publication Year :
- 2021
-
Abstract
- 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.<br />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.<br />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.<br />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.
- Subjects :
- Adrenergic beta-Antagonists pharmacokinetics
Adrenergic beta-Antagonists pharmacology
Animals
Anticonvulsants pharmacokinetics
Avoidance Learning drug effects
Brain metabolism
Disease Models, Animal
Dose-Response Relationship, Drug
Drug Interactions
Female
Memory, Long-Term drug effects
Mice
Sotalol pharmacokinetics
Sotalol pharmacology
Tissue Distribution
Adrenergic beta-Antagonists administration & dosage
Anticonvulsants pharmacology
Seizures drug therapy
Sotalol administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 2299-5684
- Volume :
- 73
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Pharmacological reports : PR
- Publication Type :
- Academic Journal
- Accession number :
- 33492655
- Full Text :
- https://doi.org/10.1007/s43440-020-00210-2