title: Influence of (S)-ketamine on human motor cortex excitability.
abstract: Previous studies demonstrated a reduction of motor cortical excitability through pharmacological NMDA receptor blockage. Interestingly, subanesthetic doses of racemic ketamine, a non-competitive NMDA receptor antagonist, had no effects on intracortical excitability evoked by transcranial magnetic stimulation. In this study, we aimed to substantiate these findings by using the more active enantiomer (S)-ketamine. (S)-ketamine has a threefold higher affinity for the NMDA receptor, but relatively little is known about its specific effects on human motor cortex excitability. Eleven healthy subjects (two female) participated in a randomized, double-blind, placebo-controlled cross-over study with four treatment conditions: either placebo or one of three subanesthetic doses of intravenous (S)-ketamine (serum target 10, 30 and 50 ng/ml, respectively). We assessed intracortical inhibition and facilitation using a paired-pulse TMS-paradigm. Resting motor threshold and cortical silent period were assessed as additional parameters. Solely at highest (S)-ketamine concentrations, intracortical inhibition was significantly reduced and intracortical facilitation strongly tended to be enhanced. In addition, we found a tendency to a prolonged silent period, while resting motor threshold was unaffected. We conclude that subanesthetic doses of (S)-ketamine show an enhancement on excitability in human motor cortex. Similar to findings using the racemic mixture of ketamine, the effect may be due to an increase in non-NMDA glutamatergic transmission which outweighs the NMDA receptor blockade.
authors.affiliation: Department of Neurology, Ruhr-University Bochum, BG-Kliniken Bergmannsheil, Bochum, Germany. oliver.hoeffken@ruhr-uni-bochum.de
authors.forename: Oliver
authors.initials: O
authors.lastname: Höffken
authors.forename: Ida S
authors.initials: IS
authors.lastname: Haussleiter
authors.forename: Andrea
authors.initials: A
authors.lastname: Westermann
authors.forename: Jörn
authors.initials: J
authors.lastname: Lötsch
authors.forename: Christoph
authors.initials: C
authors.lastname: Maier
authors.forename: Martin
authors.initials: M
authors.lastname: Tegenthoff
authors.forename: Peter
authors.initials: P
authors.lastname: Schwenkreis
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004576:Electromyography; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007649:Ketamine / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D009044:Motor Cortex / Q000187:drug effects*; D013237:Stereoisomerism; D050781:Transcranial Magnetic Stimulation; D055815:Young Adult
chemical_list: D018691:Excitatory Amino Acid Antagonists; D007649:Ketamine