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.