BACKGROUND AND PURPOSE: Felbamate is a new dicarbamate anticonvulsant with low toxicity currently being investigated in human clinical epilepsy trials. In this study, we examined the protective effects of felbamate against hypoxia. METHODS: We exposed paired rat hippocampal slices to hypoxia with and without felbamate treatment while monitoring the CA1-evoked population spike. RESULTS: Felbamate provided dose-dependent neuroprotection against hypoxia at concentrations of 45 mg/l and greater (p less than 0.05). At a felbamate concentration of 300 mg/l, recovery of CA1 evoked population spike amplitude after hypoxic exposure was 99% compared with 0.5% for unmedicated paired slices. The appearance and disappearance of the hypoxic injury potential was delayed in slices treated with 300 and 400 mg/l (p less than 0.05). CONCLUSIONS: In this model of hypoxia, felbamate provided neuroprotection against hypoxia at concentrations similar to serum felbamate levels currently being used in human clinical epilepsy trials.
BACKGROUND AND PURPOSE:Felbamate is a new dicarbamate anticonvulsant with low toxicity currently being investigated in human clinical epilepsy trials. In this study, we examined the protective effects of felbamate against hypoxia. METHODS: We exposed paired rat hippocampal slices to hypoxia with and without felbamate treatment while monitoring the CA1-evoked population spike. RESULTS:Felbamate provided dose-dependent neuroprotection against hypoxia at concentrations of 45 mg/l and greater (p less than 0.05). At a felbamate concentration of 300 mg/l, recovery of CA1 evoked population spike amplitude after hypoxic exposure was 99% compared with 0.5% for unmedicated paired slices. The appearance and disappearance of the hypoxic injury potential was delayed in slices treated with 300 and 400 mg/l (p less than 0.05). CONCLUSIONS: In this model of hypoxia, felbamate provided neuroprotection against hypoxia at concentrations similar to serum felbamate levels currently being used in human clinical epilepsy trials.
Authors: P A Ferchmin; Dinely Pérez; Brenda L Cuadrado; Marimée Carrasco; Antonio H Martins; Vesna A Eterović Journal: Neurochem Res Date: 2015-10-05 Impact factor: 3.996