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Titolo:
Neurotoxic/neuroprotective profile of carbamazepine, oxcarbazepine and twonew putative antiepileptic drugs, BIA 2-093 and BIA 2-024
Autore:
Ambrosio, AF; Silva, AP; Araujo, I; Malva, JO; Soares-da-Silva, P; Carvalho, AP; Carvalho, CM;
Indirizzi:
Univ Coimbra, Dept Cell Biol, Ctr Neurosci, P-3004517 Coimbra, Portugal Univ Coimbra Coimbra Portugal P-3004517 sci, P-3004517 Coimbra, Portugal Univ Coimbra, Fac Med, Biochem Lab, P-3004517 Coimbra, Portugal Univ Coimbra Coimbra Portugal P-3004517 Lab, P-3004517 Coimbra, Portugal BIAL, Dept Res & Dev, P-4785 S Mamede Do Coronado, Portugal BIAL S MamedeDo Coronado Portugal P-4785 S Mamede Do Coronado, Portugal
Titolo Testata:
EUROPEAN JOURNAL OF PHARMACOLOGY
fascicolo: 2, volume: 406, anno: 2000,
pagine: 191 - 201
SICI:
0014-2999(20001013)406:2<191:NPOCOA>2.0.ZU;2-N
Fonte:
ISI
Lingua:
ENG
Soggetto:
CEREBELLAR GRANULE CELLS; METHYL-D-ASPARTATE; HIPPOCAMPAL-NEURONS; ANTICONVULSANTS; PHENYTOIN; CA2+; NEUROTOXICITY; PHARMACOLOGY; PROTECTION; PREVENTION;
Keywords:
antiepileptic drug; neurotoxicity; neuroprotection; apoptosis;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
36
Recensione:
Indirizzi per estratti:
Indirizzo: Carvalho, CM Univ Coimbra, Dept Cell Biol, Ctr Neurosci, P-3004517 Coimbra, Portugal Univ Coimbra Coimbra Portugal P-3004517 7 Coimbra, Portugal
Citazione:
A.F. Ambrosio et al., "Neurotoxic/neuroprotective profile of carbamazepine, oxcarbazepine and twonew putative antiepileptic drugs, BIA 2-093 and BIA 2-024", EUR J PHARM, 406(2), 2000, pp. 191-201

Abstract

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 causednuclear chromatin condensation in some neurons, which is characteristic ofapoptosis, and increased the activity of caspase-3-like enzymes, mainly inneurons treated with carbamazepine and oxcarbazepine. The toxic effect caused by carbamazepine was not mediated by N-methyl-D-aspartate (NMDA) or by alpha-amino-3-hydroxy5-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. (C) 2000 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/07/20 alle ore 18:50:41