Vague effects of chronic topiramate administration on maximal electroshock-induced seizures in mice

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. (C) 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.