PhD Scientific Days 2026

Pharmaceutical Sciences and Health Technologies 4.

Distinct EEG Signatures of Ketamine Enantiomers Reflecting Their Divergent Therapeutic Potential

Előadó neve

Ms. Pothorszki, Dóra, MSc

Neptune code

GX3NWE

Előadó munkahelye

Semmelweis University - Department of Pharmacodynamics

Előadó telefonszáma

+36204086499

Előadó e-mail címe

pothorszki.dora@phd.semmelweis.hu

Az előadás címe

Distinct EEG Signatures of Ketamine Enantiomers Reflecting Their Divergent Therapeutic Potential

Szerző(k) neve és munkahelye

Dóra Pothorszki¹, Szabolcs Koncz¹, Noémi Papp¹, György Bagdy¹

1: Semmelweis University - Department of Pharmacodynamics

Bemutatás módja

Szóbeli

Szekció

Pharmaceutical Sciences and Health Technologies 4.

Language of the presentation

English

Preferred session

Pharmaceutical Sciences and Health Technologies

Összefoglaló szövege

Introduction

Racemic ketamine and (S)-ketamine are proven rapid-acting antidepressants. Regarding (R)-ketamine, clinical trials and our own preclinical rat studies failed to confirm antidepressant effect at the doses tested. However, (R)-ketamine has gained significant interest for other indications in recent years, showing therapeutic potential in animal models of cognitive impairment, Parkinson’s disease, and multiple sclerosis.

Aims

The aim was to identify ketamine enantiomer-specific quantitative electroencephalography (qEEG) biomarkers that could be connected to their divergent therapeutic applications.

Methods

Male Wistar rats were implanted with EEG and neck muscle electromyography (EMG) electrodes. Following a recovery period, animals received an intraperitoneal injection of either (S)-ketamine, (R)-ketamine (7.5, 15, or 30 mg/kg), or vehicle at the start of the passive phase and EEG, EMG, and motility were recorded for 23 hours. qEEG analysis was performed to evaluate the effects on various frequency bands.

Result

(S)-ketamine induced the "gamma-delta shift": an acute increase of gamma power (30-60 Hz) during wakefulness followed by a subsequent elevation of delta power (1-4 Hz) during NREM sleep once gamma levels normalized. (R)-ketamine only exhibited the gamma-enhancing effect at high doses and failed to induce a delta-increase. In contrast, (R)-ketamine, but not (S)-ketamine, dose-dependently and sustainably increased EEG theta power (5-9 Hz) during both wakefulness and REM sleep, throughout the 23-hour recording, peaking in the 7-8 Hz frequency range.

Conclusion

Our findings reveal distinct EEG signatures for the two enantiomers, suggesting a divergence in their underlying neural mechanisms. The gamma-delta shift appears to be a specific qEEG marker for (S)-ketamine, potentially associated with rapid antidepressant-like activity. In contrast, the sustained theta modulation induced by (R)-ketamine may serve as a biomarker for its unique hippocampal actions, which could be linked to its cognitive-enhancing effects.

Funding

Grant: NAP2022-I-4/2022, TKP2021-EGA-25
The publication was prepared also with the support of the Richter Gedeon Talentum Foundation established by Richter Gedeon Plc. in concordance with the framework of the Richter Gedeon PhD Scholarship received by Dóra Pothorszki.

University

Semmelweis University

Supervisor

Dr. György Bagdy

Publication of my abstract

I do not give consent to the publication of my abstract on the website of the congress.

phd.section.field

in doctoral studies after complex exam (PhD)

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem hagyta jóvá

Előadó

7495

Start

16:45

End

16:55