We investigated and compared the toxicity profile, as well as possible neuroprotective effects, of some antiepileptic drugs in cultured Ž . Ž . w x rat hippocampal neurons. We used two novel carbamazepine derivatives, S -y -10-acetoxy-10,11-dihydro-5H-dibenz b,f azepine-5-Ž . w x Ž . 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 Ž . Ž . 3-4,5-dimethylthiazol-2-yl -2,5-diphenyl MTT assay, as well as by analysing morphology and nuclear chromatin condensation Ž . propidium iodide staining , after hippocampal neurons were exposed to the drugs for 24 h. The putative antiepileptic drugs, BIA 2-093 or Ž . BIA 2-024 at 300 mM , 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 Ž . oxcarbazepine. The toxic effect caused by carbamazepine was not mediated by N-methyl-D-aspartate NMDA or by a-amino-3-hydroxy-Ž . 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. q