Reduction of voltage-operated sodium currents by the anticonvulsant drug sulthiame

The effect of the sulfonamide derivative sulthiame (Ospolot (R)) on voltage -operated sodium channels was investigated in acutely isolated neurons from the guinea pip hippocampus using the whole-cell patch-clamp technique. Sul thiame in a concentration of 10 mug/ml reduced the inactivating sodium curr ents without affecting potassium currents. The effect was not dependent on voltage. At therapeutic concentration of I to 10 mug/ml sodium currents wer e reduced by 13 to 25% of control. Reductions of this size (induced by the specific sodium channel blocker tetrodotoxin or by 10 mug/ml sulthiame itse lf) impaired repetitive generation of action potentials and reduced the max imum discharge frequency by 20 to 40%. In summary, the anticonvulsant drug sulthiame exerts blocking effects on sodium channels which can he assumed t o be anticonvulsant and to be different from the effects induced by blockad e of carbonic anhydrase. (C) 2001 Elsevier Science B.V. All rights reserved .