Levetiracetam influences human motor cortex excitability mainly by modulation of ion channel function--a TMS study.
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.
Reis
Janine
J
Interdisciplinary Epilepsy-Center, Department of Neurology, Philipps-University, 35033 Marburg, Germany.
Wentrup
Andreas
A
Hamer
Hajo M
HM
Mueller
Hans-Helge
HH
Knake
Susanne
S
Tergau
Frithjof
F
Oertel
Wolfgang H
WH
Rosenow
Felix
F
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
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