Abstract
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 ω-Conotoxin GVIA. After 30 min perfusion of the slices with LEV 32 μM, 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.
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