Reduction of voltage-operated sodium currents by the anticonvulsant drug sulthiame.
The effect of the sulfonamide derivative sulthiame (Ospolot) on voltage-operated sodium channels was investigated in acutely isolated neurons from the guinea pig hippocampus using the whole-cell patch-clamp technique. Sulthiame in a concentration of 10 microg/ml reduced the inactivating sodium currents without affecting potassium currents. The effect was not dependent on voltage. At therapeutic concentration of 1 to 10 microg/ml sodium currents were reduced by 13 to 25% of control. Reductions of this size (induced by the specific sodium channel blocker tetrodotoxin or by 10 microg/ml sulthiame itself) impaired repetitive generation of action potentials and reduced the maximum discharge frequency by 20 to 40%. In summary, the anticonvulsant drug sulthiame exerts blocking effects on sodium channels which can be assumed to be anticonvulsant and to be different from the effects induced by blockade of carbonic anhydrase.
Madeja
M
M
Institut für Physiologie, Robert-Koch-Str. 27a, 48149, Münster, Germany. madejam@ghst.de
Wolf
C
C
Speckmann
E J
EJ
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D006168:Guinea Pigs; D006624:Hippocampus / Q000166:cytology; D017136:Ion Transport / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D026902:Potassium Channel Blockers; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D012964:Sodium / Q000378:metabolism*; D026941:Sodium Channel Blockers; D013843:Thiazines / Q000494:pharmacology*; D000096926:Benzenesulfonamides
D000927:Anticonvulsants; D011188:Potassium; D026902:Potassium Channel Blockers; D012964:Sodium; D026941:Sodium Channel Blockers; D013843:Thiazines; C084593:sulthiame; D000096926:Benzenesulfonamides