Effect of levetiracetam on epileptiform discharges in human neocortical slices.
OBJECTIVE
The anticonvulsant effects of the novel antiepileptic drug (AED) levetiracetam (LEV) were tested in neocortical slice preparations from 23 patients who underwent surgery for the treatment of refractory epilepsy.


METHODS
Slices were used to evaluate the effects of LEV on two different models of epilepsy: low-Mg2+-induced untriggered and bicuculline-evoked stimulus-triggered epileptiform burst discharges and spontaneously appearing rhythmic sharp waves.


RESULTS
LEV (0.1-1 mM) did not influence spontaneously appearing rhythmic sharp waves or Mg2+-free aCSF-induced epileptiform field potentials. LEV affected neither the amplitudes or duration nor the repetition rates of burst discharges in these epilepsy models. However, LEV (100-500 microM) significantly suppressed the ictal-like discharges elicited by the gamma-aminobutyric acid subtype A (GABAA)-receptor antagonist bicuculline. A marked reduction of the amplitude and duration of bicuculline-evoked field response in the presence of LEV was observed.


CONCLUSIONS
The results indicate the potential for LEV to inhibit epileptiform burst discharges in human neocortical tissue, which is consistent with its effects in animal models of epilepsy. These results also support the seizure reduction observed in clinical trials and support that this may, in part, be related to the ability of LEV to inhibit epileptiform discharges.
Gorji
Ali
A
Institut für Physiologie, Universität Münster, Münster, Germany. gorjial@uni-muenster.de
Höhling
Jorg-Michael
JM
Madeja
Michael
M
Straub
Heidrun
H
Köhling
Rüdiger
R
Tuxhorn
Ingrid
I
Ebner
Alois
A
Wolf
Peter
P
Panneck
H W
HW
Behne
F
F
Lahl
Rainer
R
Speckmann
Erwin-Joseph
EJ
D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000494:pharmacology*; D001640:Bicuculline / Q000031:analogs & derivatives* / Q000494:pharmacology; D002648:Child; D002675:Child, Preschool; D003470:Culture Media; D046508:Culture Techniques; D004558:Electric Stimulation; D004569:Electroencephalography / Q000187:drug effects*; D004827:Epilepsy / Q000503:physiopathology*; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D006801:Humans; D007223:Infant; D000077287:Levetiracetam; D008274:Magnesium / Q000502:physiology; D008297:Male; D008875:Middle Aged; D019579:Neocortex / Q000187:drug effects* / Q000503:physiopathology; D010889:Piracetam / Q000031:analogs & derivatives* / Q000494:pharmacology*
D000927:Anticonvulsants; D003470:Culture Media; C017069:bicuculline methiodide; D000077287:Levetiracetam; D008274:Magnesium; D001640:Bicuculline; D010889:Piracetam