Levetiracetam (ucb LO59) affects in vitro models of epilepsy in CA3 pyramidal neurons without altering normal synaptic transmission.
Previous behavioural and electrophysiological studies have indicated that levetiracetam (ucb LO59) acts as an anticonvulsant drug in vivo. The purpose of the present study was to investigate the effects of levetiracetam on normal synaptic transmission and epileptiform activity in vitro. Intracellular recordings were obtained from the CA3 subfield of the rat hippocampal slice preparation. Levetiracetam in a concentration of 10 microM did not influence basic cell properties or normal synaptic transmission evoked by subthreshold and suprathreshold stimuli to the commissural pathway. However, it strongly inhibited the development of epileptiform bursting by the gamma-aminobutyric acid (GABA)A-receptor antagonist bicuculline (1-30 microM). Levetiracetam also decreased the size of bursts previously established by bicuculline. In experiments in which the glutamate-receptor agonist N-Methyl-D-Aspartate (NMDA) was used to generate spontaneous bursting, levetiracetam had no effect on the size of the bursts but decreased bursting frequency. The difference in effects of levetiracetam on bicuculline- and NMDA-induced bursting appeared to be dependent on the convulsant used, since in the presence of 10 microM bicuculline, levetiracetam decreased the size of NMDA-bursts to the same extent as the size of synaptically evoked bicuculline-bursts but had little effect on bursting frequency. The results show that under our experimental conditions, levetiracetam did not alter the components of normal synaptic transmission. However, levetiracetam at the concentrations studied inhibited epileptiform bursting induced by bicuculline and NMDA in vitro in a manner consistent with the profile of an antiepileptogenic drug.
Birnstiel
S
S
Department of Pharmacology and Experimental Therapeutics, Loyola University Medical Center, Maywood, IL 60153, USA.
Wülfert
E
E
Beck
S G
SG
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D001640:Bicuculline / Q000494:pharmacology*; D004347:Drug Interactions; D004558:Electric Stimulation; D004827:Epilepsy / Q000188:drug therapy / Q000503:physiopathology*; D018756:GABA Antagonists / Q000494:pharmacology*; D000077287:Levetiracetam; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008954:Models, Biological; D010889:Piracetam / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D017966:Pyramidal Cells / Q000187:drug effects* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects*
D000927:Anticonvulsants; D018756:GABA Antagonists; D000077287:Levetiracetam; D001640:Bicuculline; D010889:Piracetam