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Pharmacopsychiatry 2023; 56(04): 154-161
DOI: 10.1055/a-2078-4823
Original Paper

GABAergic Effects of Etifoxine and Alprazolam Assessed by Double Pulse TMS

Marco Riebel
1   Department of Psychiatry and Psychotherapy, University of Regensburg, Germany
,
Benedikt von Pappenheim
1   Department of Psychiatry and Psychotherapy, University of Regensburg, Germany
,
Carolina Kanig
1   Department of Psychiatry and Psychotherapy, University of Regensburg, Germany
,
Caroline Nothdurfter
1   Department of Psychiatry and Psychotherapy, University of Regensburg, Germany
,
Thomas C. Wetter
1   Department of Psychiatry and Psychotherapy, University of Regensburg, Germany
,
Rainer Rupprecht
1   Department of Psychiatry and Psychotherapy, University of Regensburg, Germany
,
Jens Schwarzbach
1   Department of Psychiatry and Psychotherapy, University of Regensburg, Germany
› Author Affiliations Funding This work has been supported by the German Research Foundation (Deutsche Forschungsgemeinschaft) (DFG), project number 422179811, to RR, CN, and JS within the framework of FOR2858.
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Abstract

Introduction There is a need for novel anxiolytics with improved side effect profiles compared to benzodiazepines. A promising candidate with alternative pharmacodynamics is the translocator protein ligand, etifoxine.

Methods To get further insight into its mechanisms of action and side effects compared to the benzodiazepine alprazolam, we performed a double-blind, placebo-controlled, repeated-measures study in 36 healthy male subjects. Participants were examined for trait anxiety and side effects and underwent repeated transcranial magnetic stimulation (TMS) assessments, including motor evoked potentials (MEP), short intracortical inhibition (SICI), intracortical facilitation (ICF), and cortical silent period (CSP).

Results We observed attenuation of MEPs by alprazolam but not by etifoxine. SICI was not significantly affected by alprazolam or etifoxine. However, the response pattern indicated a lowered SICI threshold after the administration of etifoxine and alprazolam compared to the placebo. ICF and CSP were influenced by neither medication. Alprazolam led to higher sedation and subjective impairment of concentration compared to etifoxine. Individual anxiety trait scores did not affect TMS parameters.

Discussion This study indicated a favorable side effect profile of etifoxine in healthy volunteers. Moreover, it revealed differential GABA-related effects on neuromuscular function by means of TMS. The side effects and TMS profile of etifoxine are compatible with the involvement of neurosteroidogenesis and a predominant α3 subunit modulation compared to alprazolam.

Key words

TMS - TSPO - benzodiazepines - etifoxine - GABA

Supplementary Material



Publication History

Received: 07 February 2023
Received: 12 April 2023

Accepted: 13 April 2023

Article published online:
23 May 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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