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Anticonvulsant effects of selected antiepileptic drugs in mice exposed to caffeine during pregnancy and breastfeeding in the maximal electroshock-induced seizure model

100%

Miziak B., Radzik I., Czuczwar S. J.

Acta Neurobiologiae Experimentalis

2017

tom 77

nr Suppl.1

INTRODUCTION: Caffeine presence in coffee, tea and some drugs makes it the most commonly consumed stimulant drug. Available data show that consumption of caffeine during pregnancy and in the early postpartum period while breastfeeding can affect the offspring’s behaviour at the later stages of life. AIM(S): The aim was to test the impact of caffeine fed to pregnant and breastfeeding mice on the anticonvulsant activity of selected antiepileptic drugs (AEDs): sodium valproate (VPA), topiramate (TPM) and carbamazepine (CBZ), against the maximal electroshock-induced seizures (MES). METHOD(S): From the 3 day after fertilization, pregnant mice received caffeine dissolved in drinking water throughout the pregnancy, and then throughout breastfeeding. The experiments were carried out on adult offspring (mice in their 8th week of age). The control groups comprised mice, born by females that received only pure water throughout the pregnancy and then throughout breastfeeding while experimental groups – mice, born by females that drank caffeine (0.3 g/l). Seizures were induced by alternating current (25 mA, 50 Hz, stimulus duration 0.2 s) delivered by a generator via ear electrodes. Undesirable effects of the combined treatments were examined in the chimney test, passive avoidance task, and grip strength test. RESULTS: In the groups exposed to caffeine, there was a significant impairment of the anticonvulsant action of both, VPA and CBZ. The respective ED50s were increased from 155.5 (146.2–165.4) to 175.5 (164.1–187.7) and from 8.4 (6.9–10.3) to 11.6 (10.5–12.9) mg/kg, respectively. As regards TPM, no significant impact of exposure to caffeine on the effectiveness of this AED has been observed. The neurotoxic effects of AEDs were not affected by caffeine exposure. CONCLUSIONS: The experiments show that exposure to caffeine has a statistically relevant influence on the anticonvulsant action of VPA and CBZ against MES test carried out in the exposed offspring. FINANCIAL SUPPORT: DS 475.

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Isobolographic assessment of interactions between retigabine and phenytoin in the mouse maximal electroshock-induced seizure model and chimney test

51%

Zolkowska D., Zagaja M., Miziak B., Kondrat-Wrobel M. W., Zaluska K., Florek-Luszczki M., Szpringer M., Drop B., Zadrozniak M., Czuczwar S. J., Luszczki J. J.

Health Problems of Civilization

2016

tom 10

nr 4

Background. Search for beneficial combinations of antiepileptic drugs (AEDs) that can be used in patients with pharmacoresistant epilepsy, is still conducted both empirically and rationally, based on molecular mechanisms of AEDs’ action. This study was aimed at characterizing the interaction profiles for the combination of two AEDs (i.e., retigabine [RTG] and phenytoin [PHT]) in the maximal electroshock-induced seizures (MES) and chimney test (motor performance) in adult male albino Swiss mice. Material and methods. Type I isobolographic analysis was used to determine interactions for the combination of RTG with PHT (at three fixed-ratios of 1:3, 1:1 and 3:1) with respect to its anticonvulsant and acute neurotoxic effects in the MES and chimney tests, respectively. Total brain concentrations of RTG and PHT were estimated to exclude any pharmacokinetic interaction between AEDs. Results. The combination of RTG with PHT at the fixed-ratios of 1:3, 1:1 and 3:1 produced additive interactions in both, the MES and chimney tests. RTG and PHT did not affect each other their total brain concentrations in mice, confirming pharmacodynamic interaction between the investigated drugs. Conclusions. The combination of RTG with PHT was neutral suggesting that this two-drug combination might occur favorable in some patients with refractory epilepsy.

Ograniczanie wyników

1 Acta Neurobiologiae Experimentalis

1 Health Problems of Civilization

2 Czuczwar S. J.

2 Miziak B.

1 Drop B.

1 Florek-Luszczki M.

1 Kondrat-Wrobel M. W.

1 Luszczki J. J.

1 Radzik I.

1 Szpringer M.

1 Zadrozniak M.

1 Zagaja M.

1 Zaluska K.

1 Zolkowska D.

1 2017

1 2016

Wyniki wyszukiwania

Anticonvulsant effects of selected antiepileptic drugs in mice exposed to caffeine during pregnancy and breastfeeding in the maximal electroshock-induced seizure model

Isobolographic assessment of interactions between retigabine and phenytoin in the mouse maximal electroshock-induced seizure model and chimney test