PP07.1 - 2308: Attenuation of the anticonvulsant effects of classical antiepileptic drugs against electroshock-induced convulsions in mice fed the ketogenic diet

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• 作者：I. Zarnowska ; J. Luszczki ; S.J. Czuczwar ; P. Wlaz ; M. Gasior
• 刊名：European Journal of Paediatric Neurology
• 出版年：2015
• 出版时间：May 2015
• 年：2015
• 卷：19
• 期：supp_S1
• 页码：S55-S56
• 全文大小：114 K

文摘

To investigate whether the KD could affect the anticonvulsant activity and pharmacokinetic properties of several AEDs in a model of generalized tonic-clonic epilepsy.

Methods

Male Swiss mice weighing 20–25 g were used for experiments. Mice were fed the KD for 2 weeks (bioserv.com/product/F3666.html">http://www.bioserv.com/product/F3666.html, 6:1 ratio of fat to protein + carbohydrates); control mice were receiving a standard rodent diet. The following AEDs were studied: carbamazepine, phenobarbital, phenytoin, and valproate. Electroconvulsions were induced by applying an alternating current via ear-clip electrodes in two methodologically different experimental approaches: maximal electroshock seizure threshold (MEST) test and maximal electroshock seizure (MES) test.

Results

The KD decreased the electroconvulsive threshold in the MEST test in mice, i.e. 47% decrease of the CS50 value from 7.29 to 3.86 mA, p<0.05). Also, the KD decreased potencies of all tested AEDs as reflected by their increased ED50 values in the MES test (p<0.05). Specifically, ED50 values increased from 11.4 to 17.7 mg/kg for carbamazepine, from 26.9 to 37.4 mg/kg for phenobarbital, from 11.3 to 194 mg/kg for phenytoin, and from 265.9 to over 400 mg/kg for valproate in mice fed the normal and KD diet, respectively). Exposure to the KD for two weeks had no effect on the brain levels of the four AEDs studied.

Conclusion

Though the KD has proven efficacy in clinical practice, it lowers the electroconvulsive threshold in the MEST test in mice. Moreover, the KD attenuates the anticonvulsant efficacy of the AEDs tested. This paradoxical effect of AEDs losing their anticonvulsant efficacy in mice fed the KD may be reflective of a higher energy state produced by the KD leading to a facilitated spread of electroconvulsions in the brain. It is concluded that that the MES and MEST tests may not be suitable for studying the anticonvulsant properties of the KD in mice.