title: Effect of levetiracetam on epileptiform discharges in human neocortical slices.
abstract: 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.
authors.affiliation: Institut für Physiologie, Universität Münster, Münster, Germany. gorjial@uni-muenster.de
authors.forename: Ali
authors.initials: A
authors.lastname: Gorji
authors.forename: Jorg-Michael
authors.initials: JM
authors.lastname: Höhling
authors.forename: Michael
authors.initials: M
authors.lastname: Madeja
authors.forename: Heidrun
authors.initials: H
authors.lastname: Straub
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Köhling
authors.forename: Ingrid
authors.initials: I
authors.lastname: Tuxhorn
authors.forename: Alois
authors.initials: A
authors.lastname: Ebner
authors.forename: Peter
authors.initials: P
authors.lastname: Wolf
authors.forename: H W
authors.initials: HW
authors.lastname: Panneck
authors.forename: F
authors.initials: F
authors.lastname: Behne
authors.forename: Rainer
authors.initials: R
authors.lastname: Lahl
authors.forename: Erwin-Joseph
authors.initials: EJ
authors.lastname: Speckmann
mesh_terms: 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*
chemical_list: D000927:Anticonvulsants; D003470:Culture Media; C017069:bicuculline methiodide; D000077287:Levetiracetam; D008274:Magnesium; D001640:Bicuculline; D010889:Piracetam