Desynchronizing effect of levetiracetam on epileptiform responses in rat hippocampal slices.
The effect of levetiracetam on neuronal hypersynchrony and hyperexcitability was examined using simultaneous extra- and intracellular recordings in rat brain slices perfused with a high K+/low Ca2+ (HKLC) fluid. These findings were compared to results obtained with carbamazepine, valproate and clonazepam. The HKLC milieu induces in hippocampal CA3 area, spontaneous interictal bursts and epileptiform responses. Levetiracetam decreased the number of population spikes per extracellular response but did not affect the number of action potentials per intracellular burst. This contrasts the effects of the reference antiepileptic drugs, which depressed both the extracellular and the intracellular bursts. These results indicate that levetiracetam is distinct from classical antiepileptic drugs by a relatively selective effect on collective neuronal responses, rather than on single neuron activity and suggests a potentially novel desynchronizing effect that probably contributes to its antiepileptic action.
Niespodziany
Isabelle
I
UCB SA Pharma Sector, Preclinical CNS Research, Chemin du Foriest, Braine-l'Alleud, Belgium. isabelle.niespodziany:ucb-group.com
Klitgaard
Henrik
H
Margineanu
Doru Georg
DG
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D000077287:Levetiracetam; D008297:Male; D010889:Piracetam / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000077287:Levetiracetam; D010889:Piracetam