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Vague effects of chronic topiramate administration on maximal electroshock-induced seizures in mice
Monika Banach1, Paweł Szpot2, Grzegorz Buszewicz2
1Independent Unit of Experimental Neuropathophysiology, Department of Pathophysiology, Medical University of Lublin, Lublin, Poland.
Background:
Almost all experimental studies evaluating interactions between antiepileptic and non-antiepileptic drugs are based on their single administration, whereas epileptic patients require chronic pharmacotherapy. Herein, we attempted to figure out whether single and repeated administration of topiramate leads to the same anticonvulsant and undesired effects.
Methods:
Experiments were conducted in the model of maximal electroshock in mice. Motor coordination was evaluated in the chimney test. Brain concentrations of topiramate were determined by high-performance liquid chromatography and triple quadrupole mass spectrometry.
Results:
The anticonvulsant activity of topiramate administered once or twice a day for 7 days did not significantly differ from the respective effect of topiramate given acutely in a single injection. However, calculating of 50% effective doses for topiramate applied in 14-days protocol (once or two times a day) was impossible. The antiepileptic administered at the dose range of 80-150 mg/kg did not offer protection in more than 50% of mice. This phenomenon cannot be attributed to pharmacokinetic events, because there were no significant differences between plasma and brain concentrations of topiramate after its acute and chronic administration. Topiramate (150 mg/kg) did not affect motor performance in mice.
Conclusions:
Maximal electroshock in mice does not seem to be an appropriate seizure model to test anticonvulsant effects of chronic topiramate.
Insights
Chronic topiramate administration did not alter anticonvulsant effects compared to acute doses in mice. However, the maximal electroshock seizure model proved unsuitable for evaluating long-term topiramate efficacy.
Area of Science:
- Pharmacology
- Neuroscience
- Drug Metabolism
Background:
- Epilepsy treatment necessitates chronic pharmacotherapy, yet most studies assess antiepileptic drugs based on single administrations.
- Investigating the impact of chronic topiramate administration on anticonvulsant and adverse effects is crucial for clinical relevance.
Purpose of the Study:
- To determine if single and repeated administration of topiramate produce similar anticonvulsant and undesired effects in a mouse model.
- To evaluate the suitability of the maximal electroshock seizure model for assessing chronic topiramate therapy.
Main Methods:
- Maximal electroshock seizure model in mice to assess anticonvulsant activity.
- Chimney test to evaluate motor coordination.
- High-performance liquid chromatography and triple quadrupole mass spectrometry for determining brain concentrations of topiramate.
Main Results:
- Anticonvulsant activity of topiramate after 7 days of repeated administration did not significantly differ from acute administration.
- Calculating 50% effective doses for topiramate after 14 days of administration was impossible, indicating reduced efficacy.
- No significant differences in plasma and brain concentrations of topiramate were observed between acute and chronic administration, ruling out pharmacokinetic changes.
Conclusions:
- The maximal electroshock seizure model is not appropriate for evaluating the anticonvulsant effects of chronic topiramate treatment.
- Further research is needed to identify suitable models for assessing long-term antiepileptic drug efficacy.
