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Fundam Clin Pharmacol ; 25(4): 485-92, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20636364

RESUMO

This study was aimed at investigating the anticonvulsant activity of lipoic acid (LA) against pilocarpine-induced seizures as well as the effects of this metabolic antioxidant on the hippocampal extracellular concentrations of amino acid neurotransmitters glutamate, aspartate, glycine and glutamate and γ-aminobutyric acid (GABA). In vivo microdialysis demonstrated that an intraperitoneal administration of pilocarpine induced a pronounced increment of hippocampal glutamate and aspartate concentrations, whereas no significant change was observed in the levels of glycine or GABA. LA (10, 20 or 30 mg/kg) pretreatment completely blocked pilocarpine-evoked increases in extracellular glutamate and aspartate concentrations. Significant reductions in hippocampal GABA and glycine concentrations were also observed although not as pronounced as those shown by glutamate and aspartate. Based on the finding that LA protected rats against pilocarpine-induced seizures, it could be suggested that the reduction in inhibitory amino acid neurotransmitters levels was comparatively minor and offset by a more pronounced reduction in glutamate and aspartate extracellular concentrations. Therefore, the fact that LA could drastically reduce pilocarpine-induced increases in glutamate and aspartate should account, at least partly, for its anticonvulsant activity observed in pilocarpine-induced seizure in rats.


Assuntos
Aminoácidos Excitatórios/líquido cefalorraquidiano , Hipocampo/metabolismo , Pilocarpina/farmacologia , Convulsões/metabolismo , Ácido Tióctico/farmacologia , Animais , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Ácido Aspártico/líquido cefalorraquidiano , Diálise/métodos , Ácido Glutâmico/líquido cefalorraquidiano , Glicina/líquido cefalorraquidiano , Hipocampo/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Convulsões/induzido quimicamente , Convulsões/mortalidade , Convulsões/fisiopatologia , Convulsões/prevenção & controle , Estado Epiléptico/induzido quimicamente , Estado Epiléptico/metabolismo , Estado Epiléptico/mortalidade , Estado Epiléptico/fisiopatologia , Estado Epiléptico/prevenção & controle , Análise de Sobrevida , Ácido Tióctico/uso terapêutico , Ácido gama-Aminobutírico/líquido cefalorraquidiano
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