Effect of caffeine on the anticonvulsant action of pregabalin against electroconvulsions in mice

Pharmacol Rep. 2022 Apr;74(2):431-437. doi: 10.1007/s43440-022-00356-1. Epub 2022 Feb 16.

Abstract

Background: Experimental data indicate that caffeine (CAF) can reduce the anticonvulsant activity of antiepileptic drugs (AEDs) in animal models of seizures. The purpose of the current study was to examine the effect of CAF on the protective action of pregabalin (PGB) against electroconvulsions in mice.

Methods: Maximal electroshock seizure (MES) test was used in the current study. In addition, the combined treatment with CAF and PGB was assessed in the passive avoidance task (long-term memory) and the chimney test (motor coordination). Drugs were injected intraperitoneally (ip) as single injections. CAF was administered at doses reported to compromise the anticonvulsant action of AEDs in mice.

Results: CAF at a dose of 23.1 mg/kg reduced the anticonvulsant action of PGB in the MES test. The brain concentration of PGB was not significantly changed by CAF and vice versa. In the chimney test, CAF (23.1 mg/kg) protected mice against PGB-induced motor coordination impairment.

Conclusions: Regarding seizure control, it might be suggested that patients with epilepsy treated with PGB should avoid taking CAF. The estimated total brain concentration of PGB and CAF does not suggest a pharmacokinetic interaction as an explanation for these results.

Keywords: Antiepileptic drugs; Caffeine; Chimney test; Passive avoidance test; Seizures.

MeSH terms

  • Animals
  • Anticonvulsants* / therapeutic use
  • Brain
  • Caffeine*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Electroshock
  • Humans
  • Mice
  • Pregabalin / pharmacology
  • Seizures / drug therapy

Substances

  • Anticonvulsants
  • Caffeine
  • Pregabalin