title: Effect of a single dose of retigabine in cortical excitability parameters: A cross-over, double-blind placebo-controlled TMS study.
abstract: Antiepileptic drugs (AEDs) decrease the occurrence of epileptic seizures and modulate cortical excitability through several mechanisms that likely interact. The modulation of brain excitability by AEDs is believed to reflect their antiepileptic action(s) and could be used as a surrogate marker of their efficacy. Transcranial magnetic stimulation (TMS) is one of the best noninvasive methods to study cortical excitability in human subjects. Specific TMS parameters can be used to quantify the various mechanisms of action of AEDs. A new AED called retigabine increases potassium efflux by changing the conformation of KCNQ 2-5 potassium channels, which leads to neuronal hyperpolarisation and a decrease in excitability.
  
  
  
  The purpose of this study is to investigate the effect of retigabine on cortical excitability. Based on the known mechanisms of action of retigabine, we hypothesized that the oral intake of retigabine would increase the resting motor threshold (RMT).
  
  
  
  Fifteen healthy individuals participated in a placebo-controlled, double-blind, randomised, clinical trial (RCT). The primary outcome measure was the RMT quantified before and after oral intake of retigabine. Several secondary TMS outcome measures were acquired.
  
  
  
  The mean RMT, active motor threshold (AMT) and intensity to obtain a 1mV peak-to-peak amplitude potential (SI1mV) were significantly increased after retigabine intake compared to placebo (RMT: P=0.039; AMT: P=0.014; SI1mV: P=0.019). No significant differences were found for short-interval intracortical inhibition/intracortical facilitation (SICI/ICF), long-interval intracortical inhibition (LICI) or short-interval intracortical facilitation (SICF).
  
  
  
  A single dose of retigabine increased the RMT, AMT and S1mV in healthy individuals. No modulating intracortical facilitation or inhibition was observed. This study provides the first in vivo demonstration of the modulating effects of retigabine on the excitability of the human brain, and the results are consistent with the data showing that retigabine hyperpolarizes neurons mainly by increasing potassium conductance.
authors.affiliation: Université catholique de Louvain (UCL), CHU UCL Namur, Department of Neurology, Avenue Dr G. Thérasse, B5530 Yvoir, Belgium; Université catholique de Louvain (UCL), Institute of NeuroSciences (IoNS), Avenue Hippocrate, 54 Bte 54.10, 1200 Brussels, Belgium. Electronic address: michel.ossemann@uclouvain.be.
authors.forename: Michel
authors.initials: M
authors.lastname: Ossemann
authors.affiliation: Université catholique de Louvain (UCL), CHU UCL Namur, Department of Neurology, Avenue Dr G. Thérasse, B5530 Yvoir, Belgium; Université catholique de Louvain (UCL), Institute of NeuroSciences (IoNS), Avenue Hippocrate, 54 Bte 54.10, 1200 Brussels, Belgium.
authors.forename: Katalin
authors.initials: K
authors.lastname: de Fays
authors.affiliation: Université catholique de Louvain (UCL), CHU UCL Namur, Scientific Support Unit Avenue Dr G. Thérasse, 5530 Yvoir, Belgium.
authors.forename: Benoit
authors.initials: B
authors.lastname: Bihin
authors.affiliation: Université catholique de Louvain (UCL), CHU UCL Namur, Department of Neurology, Avenue Dr G. Thérasse, B5530 Yvoir, Belgium; Université catholique de Louvain (UCL), Institute of NeuroSciences (IoNS), Avenue Hippocrate, 54 Bte 54.10, 1200 Brussels, Belgium.
authors.forename: Yves
authors.initials: Y
authors.lastname: Vandermeeren
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D000927:Anticonvulsants / Q000494:pharmacology*; D002219:Carbamates / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004576:Electromyography; D005260:Female; D006801:Humans; D008297:Male; D009044:Motor Cortex / Q000187:drug effects* / Q000502:physiology*; D009068:Movement / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000502:physiology; D010655:Phenylenediamines / Q000494:pharmacology*; D012146:Rest; D050781:Transcranial Magnetic Stimulation
chemical_list: D000927:Anticonvulsants; D002219:Carbamates; D010655:Phenylenediamines; C101866:ezogabine
keywords: Cortical excitability; Human; Retigabine; TMS