Levetiracetam inhibits the high-voltage-activated Ca2+ current in pyramidal neurones of rat hippocampal slices

The effect of the new antiepileptic drug levetiracetam (LEV; KEPPRA(TM)) on the neuronal high-voltage-activated (HVA) Ca2+ 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 Ca2+ currents. The HVA current, activated by steadily increasing voltage-ramps, was reversibly eliminated by Cd2+ and depressed by either nimodipine, or omega -Conotoxin GVIA. After 30 min perfusion of the slices with LEV 32 muM, 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 Ca2+ current, produced by LEV at a clinically relevant concentration, might contribute to the antiepileptic action of the drug. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.