Inhibition of neuronal hypersynchrony in vitro differentiates levetiracetam from classical antiepileptic drugs

Field potentials were recorded from rat hippocampal slices in order to compare the electrophysiological action of the new antiepileptic drug (AED), levetiracetam (LEV), with that of the classical AEDs, valproate, clonazepam and carbamazepine, on epileptiform responses induced by a ‘high K+–low Ca2+’ perfusion fluid. Increasing [K+] from 3 to 7.5 mM and decreasing [Ca2+] from 2.4 to 0.5 mM, in the bathing fluid, produced population spikes (PSs) of increasing amplitudes in the CA3 area of the slices, repetitive PSs evoked by single stimuli, and spontaneous bursts. Clinically relevant concentrations of LEV, 32 and 100μ M, consistently reduced the second (PS2) and third (PS3) population spikes, and the number (N) of repetitive PSs per evoked response. Levetiracetam 32 μ M also opposed the increase in amplitude of the first PS (Δ PS1). Neither valproate 1 mM, nor clonazepam 1μ M, nor carbamazepine 50 μ M, produced any decrease in Δ PS1and in PS2, but all decreased N. These results show that LEV contrasts to reference AEDs by its ability to antagonize neuronal (hyper)synchronization, in the highly seizure-prone CA3 area of rat hippocampal slices.