title: Levetiracetam influences human motor cortex excitability mainly by modulation of ion channel function--a TMS study.
abstract: OBJECTIVE
  Levetiracetam (LEV) is a new compound with anticonvulsive efficacy in focal and generalized epilepsies. Recent in vitro studies suggest LEV to act as a selective N-type-calcium-channel blocker.
  
  
  METHODS
  We used transcranial magnetic stimulation (TMS) in order to investigate if ion-channel blockade is relevant to the inhibitory CNS effects of LEV in vivo and if motor thresholds (MTs) are a valid TMS parameter to detect this mode of action. In a double blind, placebo-controlled, crossover study, the effects of single oral doses of 500 and 2000 mg LEV on motor thresholds, recruitment curves (REC), cortical induced silent period (CSP) and on intracortical inhibition (ICI) and facilitation (ICF) were studied in 10 healthy subjects.
  
  
  RESULTS
  A significant increase of motor thresholds was noticed after 2000 mg LEV as compared to placebo. The recruitment curve showed a trend towards motor evoked potential (MEP) amplitude reduction after LEV. LEV had no significant effect on CSP or on intracortical excitability as measured by inhibition and facilitation.
  
  
  CONCLUSIONS
  We conclude that the modulation of ion-channel function, reflected by motor threshold elevation and a trend towards recruitment curve suppression, is relevant to the inhibitory CNS effects of LEV in vivo, and therefore, may contribute to the anticonvulsive efficacy of LEV. GABAergic or glutamatergic mechanisms seem to be less important in vivo as measured by TMS.
authors.affiliation: Interdisciplinary Epilepsy-Center, Department of Neurology, Philipps-University, 35033 Marburg, Germany.
authors.forename: Janine
authors.initials: J
authors.lastname: Reis
authors.forename: Andreas
authors.initials: A
authors.lastname: Wentrup
authors.forename: Hajo M
authors.initials: HM
authors.lastname: Hamer
authors.forename: Hans-Helge
authors.initials: HH
authors.lastname: Mueller
authors.forename: Susanne
authors.initials: S
authors.lastname: Knake
authors.forename: Frithjof
authors.initials: F
authors.lastname: Tergau
authors.forename: Wolfgang H
authors.initials: WH
authors.lastname: Oertel
authors.forename: Felix
authors.initials: F
authors.lastname: Rosenow
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects* / Q000528:radiation effects*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004574:Electromagnetic Fields; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D006801:Humans; D007473:Ion Channels / Q000187:drug effects*; D000077287:Levetiracetam; D008297:Male; D009044:Motor Cortex / Q000187:drug effects*; D010889:Piracetam / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D011446:Prospective Studies; D011963:Receptors, GABA-A / Q000187:drug effects; D018009:Receptors, Glycine / Q000037:antagonists & inhibitors; D011999:Recruitment, Neurophysiological / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D013237:Stereoisomerism
chemical_list: D000927:Anticonvulsants; D015220:Calcium Channels; D018756:GABA Antagonists; D007473:Ion Channels; D015221:Potassium Channels; D011963:Receptors, GABA-A; D018009:Receptors, Glycine; D000077287:Levetiracetam; D010889:Piracetam