Influence of (S)-ketamine on human motor cortex excitability
- 437 Downloads
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.
Keywords(S)-ketamine TMS Motor cortex Excitability
We thank Steven L. Shafer for providing STANPUMP. The first author acknowledges support from a DFG Grant. This study was supported by a grant from the Faculty of Medicine of the Ruhr-University Bochum (FoRUM AZ F417/2004). Sources of support: Equipment: STANPUMP is freely available from the author, Steven L. Shafer, M.D., Anesthesiology Service (112A), PAVAMC, 3801 Miranda Ave., Palo Alto, CA. 94304 at http://www.opentci.org/lib/exe/fetch.php?media=code:stanpump.zip, accessed on July 3, 2012.
Conflict of interest
The authors O.H., I.H., J.L., A.W., and M.T. declare that there is no conflict of interest. C.M. received fees for consulting from Astellas Sanofi Aventis, Wyeth, Pfizer, Mundipharma, Eli Lilly. He received research funding from Pfizer, MSD, Mundipharma, Grünenthal, Astellas, Lilly. He is a member of the IMI “Europain” collaboration and industry members of this are as follows: AstraZeneca, Pfizer, Esteve, UCBPharma, Sanofi Aventis, Grünenthal, Eli Lilly, and Boehringer Ingelheim. P.S. received research funding from Bayer Health Care AG, Biogen Idec, Merck KGaA, and Teva Pharma GmbH.
- Oertel BG, Felden L, Tran PV, Bradshaw MH, Angst MS, Schmidt H, Johnson S, Greer JJ, Geisslinger G, Varney MA, Lotsch J (2010) Selective antagonism of opioid-induced ventilatory depression by an ampakine molecule in humans without loss of opioid analgesia. Clin Pharmacol Ther 87:204–211PubMedCrossRefGoogle Scholar
- Schuhfried G (2009) Daueraufmerksamkeit (DAUF) aus dem Wiener Testsystem (WTS). In: Schellig D, Drechsler R, Heinemann D, Sturm W (eds) Handbuch neuropsychologischer Testverfahren. Hogrefe, Aufmerksamkeit, Gedächtnis und exekutive Funktionen, pp 67–72Google Scholar