Effects of Levetiracetam on the Content of Neurotransmitter Amino Acids in the Brain of Rats with the Audiogenic Epileptiform Siezures

Abstract

The anticonvulsant action of novel antiepileptic drug levetiracetam (LVT) on the content of aspartate, glutamate, glycine, taurine and GABA in brain structures of Krushinsky-Molodkina (KM) rats were studied using HPLC/FD techniques. The treatment with LVT anticipated decrease of levels of glutamate, glycine and taurine produced by seizure attack. In medulla oblongata LVT prevented the elevation of GABA level induced by the audiogenic stress. Thus, the anticonvulsant action of LVT against audiogenic seizures is likely to be related to the normalizing effect upon the levels of both excitatory and inhibitory neurotransmitter amino acid in the frontal cortex and medulla oblongata of KM rats.

Keywords

levetiracetam (Keppra) / neurotransmitter amino acids / audiogenic seizures / Krushinsky-Molodkina (KM) rats strain

References

[1] Бадалян О.Л., Бурд С.Г., Савенков А.А. и др. Оптимизация фармакотерапии эпилепсии. Возможности применения габапентина. // Неврология. 2006. Т. 14, № 9. С. 710-713.

[2] Калинин В.В. Препарат леветирацетам (кеппра) в эпилептологии. // Ж. неврол. и психиат. 2007. Т. 107, № 3. С. 74-77.

[3] Карлов В.А., Власов П.Н. Эффективность кеппры в составе комплексной терапии при фармакорезистентной эпилепсии у взрослых. // Ж. неврол. и психиат. 2005. № 7. С. 40-44.

[4] Маликова Л.А., Федотова И.Б., Полетаева И.И., Раевский К.С. Противосудорожное действие леветирацетама при аудиогенных эпилептиформных припадках у крыс Крушинского-Молодкиной. // Эксперим. и клин. фармакол. 2007. Т. 70, № 6. С. 3-5.

[5] Раевский К.С., Маликова Л.А., Калинин В.А. Нейрональные и нейрохимические механизмы действия нового антиэпилептического препарата леветирацетама. // Эксперим. и клин. фармакол. 2007. Т. 70, № 2. С. 70-74.

[6] Семиохина А.Ф., Федотова И.Б., Полетаева И.И. Крысы линии Крушинского-Молодкиной: исследования аудиогенной эпилепсии, сосудистой патологии и поведения. // Ж. высш. нерв. деят. 2006. Т. 56, № 3. С. 298-316.

[7] Энциклопедия лекарств. Ежегодный сборник. М.: «РЛС-2007», 2006.

[8] Hanon E., Klitgaard H. Neuroprotective properties of the novel antiepileptic drug levetiracetam in the rat middle cerebral artery occlusion model of focal cerebral ischemia. // Seizure. 2001. Vol. 10, N 4. P. 287-293.

[9] De Smedt T., Raedt R., Vonck K., Boon P. Levetiracetam: the profile of a novel anticonvulsant drug-part I: preclinical data. // CNS Drug Rev. 2007. Vol. 13, N 1. P. 43-56.

[10] De Smedt T., Raedt R., Vonck K., Boon P. Levetiracetam: part II, the clinical profile of a novel anticonvulsant drug. // CNS Drug Rev. 2007. Vol. 13, N 1. P. 57-78.

[11] Dedeurwaerdere S., Vonck K., De Herdt V., et al. Neuromodulation with levetiracetam and vagus nerve stimulation in experimental animal models of epilepsy. // Acta Neurol. Belg. 2006. Vol. 106, N 2. P. 91-97.

[12] Dufour F, Nalecz K.A., Nalecz M.J., Nehlig A. Modulation of absence seizures by branched-chain amino acids: correlation with brain amino acid concentrations. // Neurosci. Res. 2001. Vol. 40, N 3. P. 255-263.

[13] Lynch B.A., Lambeng N., Nocka, et al. The synaptic vesicle protein SV2A is the binding site for the antiepileptic drug levetiracetam. // Proc. Natl. Acad. Sci. USA. 2004. Vol. 101, N 26. P. 9861-9866.

[14] Klitgaard H., Matagne A., Gobert J., Wulfert E. Evidence for a unique profile of levetiracetam in rodent models of seizures and epilepsy. // Eur.J. Pharmacol. 1998. Vol. 353 (2-3). P. 191-206.

[15] Klitgaard H. Levetiracetam: the preclinical profile of a new class of antiepileptic drugs? // Epilepsia. 2001. Vol. 42, N 4. P. 13-18

[16] Meurs A., Clinckers R., Ebinger G., et al. Seizure activity and changes in hippocampal extracellular glutamate, GABA, dopamine and serotonin. // Epilepsy Res. 2008. Vol. 78, N 1. P. 50-59.

[17] Pearson S.J., et al. Electrochemical detection of human brain transmitter amino acids by high-performance liquid chromatography of stable o-phtalaldehyde-sulphite derivatives. // J. Neuronal. Transm. 1991. Vol. 86. P. 151-157.

[18] Popova L.D. The influence of kynurenic acid on the content of excitatory and inhibitory mediators in rats with different levels of seizure susceptibility. // Ukr. Biokhim Zh. 2006. Vol. 78, N 5. P. 120-126.

[19] Sills G.J., Leach J.P., Fraser C.M., et al. Neurochemical studies with the novel anticonvulsant levetiracetam in mouse brain. // Eur.J. Pharmacol. 1997. Vol. 325, N 1. P. 35- 40.

RIGHTS & PERMISSIONS

Eco-Vector