Utilize este identificador para referenciar este registo: https://hdl.handle.net/10316/4833
Título: Neurotoxic/neuroprotective profile of carbamazepine, oxcarbazepine and two new putative antiepileptic drugs, BIA 2-093 and BIA 2-024
Autor: Ambrósio, António F. 
Silva, Ana P. 
Araújo, Inês 
Malva, João O. 
Soares-da-Silva, Patrício 
Carvalho, Arsélio P. 
Carvalho, Caetana M. 
Palavras-chave: Antiepileptic drugs; Neurotoxicity; Neuroprotection; Apoptosis
Data: 2000
Citação: European Journal of Pharmacology. 406:2 (2000) 191-201
Resumo: We investigated and compared the toxicity profile, as well as possible neuroprotective effects, of some antiepileptic drugs in cultured rat hippocampal neurons. We used two novel carbamazepine derivatives, (S)-(-)-10-acetoxy-10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide (BIA 2-093) and 10,11-dihydro-10-hydroxyimino-5H-dibenz[b,f]azepine-5-carboxamide (BIA 2-024), and compared their effects with the established compounds carbamazepine and oxcarbazepine. The assessment of neuronal injury was made by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl (MTT) assay, as well as by analysing morphology and nuclear chromatin condensation (propidium iodide staining), after hippocampal neurons were exposed to the drugs for 24 h. The putative antiepileptic drugs, BIA 2-093 or BIA 2-024 (at 300 [mu]M), only slightly decreased MTT reduction, whereas carbamazepine or oxcarbazepine were much more toxic at lower concentrations. Treatment with the antiepileptic drugs caused nuclear chromatin condensation in some neurons, which is characteristic of apoptosis, and increased the activity of caspase-3-like enzymes, mainly in neurons treated with carbamazepine and oxcarbazepine. The toxic effect caused by carbamazepine was not mediated by N-methyl--aspartate (NMDA) or by [alpha]-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA) receptors. Moreover, the antiepileptic drugs failed to protect hippocampal neurons from the toxicity caused by kainate, veratridine, or ischaemia-like conditions.
URI: https://hdl.handle.net/10316/4833
DOI: 10.1016/S0014-2999(00)00659-2
Direitos: openAccess
Aparece nas coleções:FMUC Medicina - Artigos em Revistas Internacionais

Ficheiros deste registo:
Ficheiro Descrição TamanhoFormato
file8a6865ac8b6e40d5acd3e8934d1f8517.pdf673.09 kBAdobe PDFVer/Abrir
Mostrar registo em formato completo

Citações SCOPUSTM   

58
Visto em 18/mar/2024

Citações WEB OF SCIENCETM

52
Visto em 2/mar/2024

Visualizações de página 50

565
Visto em 26/mar/2024

Downloads 10

2.264
Visto em 26/mar/2024

Google ScholarTM

Verificar

Altmetric

Altmetric


Todos os registos no repositório estão protegidos por leis de copyright, com todos os direitos reservados.