Levetiracetam inhibits the high-voltage-activated Ca(2+) current in pyramidal neurones of rat hippocampal slices.
The effect of the new antiepileptic drug levetiracetam (LEV; KEPPRA) on the neuronal high-voltage-activated (HVA) Ca(2+) current was investigated on pyramidal neurones, visually identified in the CA1 area of rat hippocampal slices. Nystatin-perforated patch clamp recordings were made under experimental conditions designed to study HVA Ca(2+) currents. The HVA current, activated by steadily increasing voltage-ramps, was reversibly eliminated by Cd(2+) and depressed by either nimodipine, or omega-Conotoxin GVIA. After 30 min perfusion of the slices with LEV 32 microM, the current decayed to 55+/-9% (mean+/-SEM; n=9) of the initial value, which is significantly (P<0.05, two-tailed t-test) lower than the rundown to 84+/-10% in a control group (n=10) of neurones. The limited, but significant depression of the neuronal HVA Ca(2+) current, produced by LEV at a clinically relevant concentration, might contribute to the antiepileptic action of the drug.
Niespodziany
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UCB S.A. Pharma Sector, Preclinical CNS Research, B-1420, Braine-l'Alleud, Belgium. tobata@oita-med.ac.jp
Klitgaard
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Margineanu
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DG
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002104:Cadmium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects* / Q000502:physiology; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology; D004827:Epilepsy / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000077287:Levetiracetam; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009553:Nimodipine / Q000494:pharmacology; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D010889:Piracetam / Q000031:analogs & derivatives / Q000494:pharmacology*; D017966:Pyramidal Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
D000927:Anticonvulsants; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002104:Cadmium; D000077287:Levetiracetam; D009553:Nimodipine; D020866:omega-Conotoxin GVIA; D010889:Piracetam