LEVETIRACETAM (UCB L059) AFFECTS IN-VITRO MODELS OF EPILEPSY IN CA3 PYRAMIDAL NEURONS WITHOUT ALTERING NORMAL SYNAPTIC TRANSMISSION

Previous behavioural and electrophysiological studies have indicated t hat levetiracetam (ucb LO59) acts as an anticonvulsant drug in vivo. T he purpose of the present study was to investigate the effects of leve tiracetam on normal synaptic transmission and epileptiform activity in vitro. Intracellular recordings were obtained from the CA3 subfield o f the rat hippocampal slice preparation. Levetiracetam in a concentrat ion of 10 mu M did not influence basic cell properties or normal synap tic transmission evoked by subthreshold and suprathreshold stimuli to the commissural pathway. However, it strongly inhibited the developmen t of epileptiform bursting by the gamma-aminobutyric acid (GABA)(A)-re ceptor antagonist bicuculline (1-30 mu M) Levetiracetam also decreased the size of bursts previously established by bicuculline. In experime nts in which the glutamate-receptor agonist N-Methyl-D-Aspartate (NMDA ) was used to generate spontaneous bursting, levetiracetam had no effe ct on the size of the bursts but decreased bursting frequency. The dif ference in effects of levetiracetam on bicuculline-and NMDA-induced bu rsting appeared to be dependent on the convulsant used, since in the p resence of 10 mu M bicuculline, levetiracetam decreased the size of NM DA-bursts to the same extent as the size of synaptically evoked bicucu lline-bursts but had little effect on bursting frequency. The results show that under our experimental conditions, levetiracetam did not alt er the components of normal synaptic transmission. However, levetirace tam at the concentrations studied inhibited epileptiform bursting indu ced by bicuculline and NMDA in vitro in a manner consistent with the p rofile of an antiepileptogenic drug.