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 microM), 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 microM, with an IC50 of 18.7 microM. In both structures, the observed inhibitions were unaffected by omega-conotoxin GVIA and omega-agatoxin IVA, suggesting that N-like channels and P-Like channels were not involved in the FBM-mediated responses. In addition, when omega-conotoxin GVIA and omega-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.

Stefani, A., Calabresi, P., Pisani, A., Mercuri, N., Siniscalchi, A., & Bernardi, G. (1996). Felbamate inhibits dihydropyridine-sensitive calcium channels in central neurons. JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 277(1), 121-127.

Felbamate inhibits dihydropyridine-sensitive calcium channels in central neurons

STEFANI, ALESSANDRO;CALABRESI, PAOLO;PISANI, ANTONIO;MERCURI, NICOLA BIAGIO;BERNARDI, GIORGIO
1996-04

Abstract

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 microM), 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 microM, with an IC50 of 18.7 microM. In both structures, the observed inhibitions were unaffected by omega-conotoxin GVIA and omega-agatoxin IVA, suggesting that N-like channels and P-Like channels were not involved in the FBM-mediated responses. In addition, when omega-conotoxin GVIA and omega-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.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/26 - Neurologia
English
Con Impact Factor ISI
Animals; Corpus Striatum; Calcium Channel Blockers; Neuroprotective Agents; Cerebral Cortex; Phenylcarbamates; Rats; omega-Conotoxin GVIA; Neurons; Rats, Wistar; Peptides; Propylene Glycols; Anticonvulsants; Male
Stefani, A., Calabresi, P., Pisani, A., Mercuri, N., Siniscalchi, A., & Bernardi, G. (1996). Felbamate inhibits dihydropyridine-sensitive calcium channels in central neurons. JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 277(1), 121-127.
Stefani, A; Calabresi, P; Pisani, A; Mercuri, Nb; Siniscalchi, A; Bernardi, G
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/88316
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