Effect of a single dose of retigabine in cortical excitability parameters: A cross-over, double-blind placebo-controlled TMS study

Michel Ossemann, Katalin De Fays, Benoît Bihin, Yves Vandermeeren

Research output: Contribution to journalArticlepeer-review

Abstract

Background

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.

Hypothesis

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).

Methods

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.

Results

The mean RMT, active motor threshold (AMT) and intensity to obtain a 1 mV peak-to-peak amplitude potential (SI1 mV) were significantly increased after retigabine intake compared to placebo (RMT: P = 0.039; AMT: P = 0.014; SI1 mV: 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).

Conclusion

A single dose of retigabine increased the RMT, AMT and S1 mV 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
Original languageEnglish
Pages (from-to)78-82
JournalEpilepsy Research
Volume126
DOIs
Publication statusPublished - Oct 2016
Externally publishedYes

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