The effect of the antiepileptic drug felbamate (FBM) on high-voltage- activated Ca++ currents was studied in cortical and neostriatal neurons acutely isolated from adult rats. Patch-clamp recordings in the whole-cell configuration were performed. Ba++ ions as the charge carrier for Ca++ channels were used. In pyramidal cortical cells, FBM dose-dependently reduced high-voltage-activated Ca++ currents in all the tested neurons. At concentrations of 30 to 100 nM, FBM already produced a significant inhibition of high-voltage-activated Ca++ currents (-6/-15%). At saturating concentrations (1-3 μM), FBM-mediated inhibition averaged 44%. The responses were fully reversible. The dose-response curves revealed IC50 of 504 nM. In striatal neurons, FBM decreased the same conductances by about 28%; the threshold dose was 1 to 2 μM, with an IC50 of 18.7 μM. In both structures, the observed inhibitions were unaffected by ω-conotoxin GVIA and ω-agatoxin IVA, suggesting that N-like channels and P-Like channels were not involved in the FBM-mediated responses. In addition, when ω-conotoxin GVIA and ω-agatoxin IVA (100 nM) were coapplied, the FBM-mediated inhibition on the remaining Ca++ currents averaged 87%. The FBM responses were occluded by micromolar concentrations of nifedipine, supporting a direct interference with dihydropyridine-sensitive channels. It is concluded that the described effect of FBM might represent an efficacious mechanism for either controlling spike discharge from epileptic foci or protecting neurons from excessive Ca++ loading. In both cases, FBM would act as a broad spectrum neuroprotective agent.
|Number of pages||7|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|Publication status||Published - Apr 1996|
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