Caffeine impairs anticonvulsant effects of levetiracetam in the maximal electroshock seizure threshold test in mice

Roman Chwedorowicz; Krzysztof Łukawski; Grzegorz Raszewski; Stanisław J. Czuczwar

doi:10.1515/jbcpp-2022-0224

Article

Caffeine impairs anticonvulsant effects of levetiracetam in the maximal electroshock seizure threshold test in mice

Roman Chwedorowicz , Krzysztof Łukawski , Grzegorz Raszewski and Stanisław J. Czuczwar

Published/Copyright: November 25, 2022

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From the journal Journal of Basic and Clinical Physiology and Pharmacology Volume 34 Issue 3

Abstract

Objectives

Caffeine is the most widely used psychoactive substance in the world. Animal studies indicate that acute caffeine exposure at high doses may induce seizures and diminish the anticonvulsant activity of antiepileptic drugs (AEDs) at much lower doses. The aim of the current study was to assess the effect of caffeine on the anticonvulsant action of levetiracetam (LEV) and vigabatrin (VGB).

Methods

The anticonvulsant activity of LEV and VGB was examined in the maximal electroshock seizure threshold test in mice (MEST test). All drugs were administered intraperitoneally by single injections, and caffeine was applied at doses capable of interfering with AEDs. Effects of caffeine exposure on AEDs were also investigated in tests of memory and motor performance.

Results

Caffeine reduced the protective effect of LEV against electroconvulsions. Total brain concentration of LEV was unaffected by caffeine as well as inversely; LEV had no significant impact on the brain caffeine concentration, suggesting a pharmacodynamic nature of the interaction between LEV and caffeine in the MEST test. VGB at applied doses did not affect the convulsive threshold. Administration of VGB, but not LEV, alone or in combination with caffeine, impaired memory retention. In the chimney test, the combined treatment with AEDs and caffeine did not cause motor coordination impairment.

Conclusions

It is suggested that caffeine may negatively affect the anticonvulsant action of LEV in patients with epilepsy.

Keywords: antiepileptic drugs; caffeine; memory; mice; motor coordination; seizures

Corresponding author: Krzysztof Łukawski, Department of Physiopathology, Institute of Rural Health, Jaczewskiego 2, 20-090 Lublin, Poland, E-mail: lukaw@mp.pl

Funding source: Institute of Rural Health, Lublin, Poland

Award Identifier / Grant number: DS 11240

Research funding: This study was supported by a grant (DS 11240) from Institute of Rural Health, Lublin, Poland.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: Authors state no conflict of interest.
Ethical approval: All animal experiments were approved by the Second Local Ethics Committee for Animal Experiments at the University of Life Sciences in Lublin. The research related to animals’ use has complied with all the relevant national regulations and institutional policies in Poland for the care and use of animals.

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Received: 2022-08-19

Accepted: 2022-11-08

Published Online: 2022-11-25

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Articles in the same Issue

https://doi.org/10.1515/jbcpp-2022-0224

Keywords for this article

antiepileptic drugs; caffeine; memory; mice; motor coordination; seizures