International Journal of Neuropsychopharmacology
September 25, 2023
Szabolcs Koncz, Noémi Papp, Dóra Pothorszki et al.
29 citations
Racemic ketamine contains two mirror-image molecules, (R)-ketamine and (S)-ketamine, which have different effects. (S)-ketamine is approved for treating major depression, but (R)-ketamine failed in recent clinical trials. In rats, a single dose of (S)-ketamine, but not (R)-ketamine, delayed the onset of rapid eye movement (REM) sleep, reduced total REM sleep time, and increased slow-wave activity during non-REM sleep. (S)-ketamine also increased wakefulness and decreased non-REM sleep in the first two hours. In chronically stressed rats, only (S)-ketamine reduced immobility in the forced swimming test, indicating antidepressant-like activity. The two enantiomers produce markedly different effects on sleep-wake patterns and behavior at the same dose.
Pharmaceuticals (Basel, Switzerland)
February 1, 2024
Dóra Pothorszki, Szabolcs Koncz, Dóra Török et al.
7 citations
In rats, (R)-ketamine, but not (S)-ketamine, dose-dependently increases EEG theta power during wakefulness and REM sleep for 23 hours. Theta rhythm originates in the hippocampus and is linked to cognitive functions, attention, and decreased anxiety. This effect on a hippocampal function not affected by (S)-ketamine may relate to neural plasticity and memory encoding.
British journal of pharmacology
June 1, 2026
Szabolcs Koncz, Dóra Pothorszki, Noémi Papp et al.
2 citations
In rats, the (S)-enantiomer of ketamine (esketamine) produces a fourfold stronger wake-promoting effect and a twofold stronger increase in gamma brainwave power during wakefulness compared to the (R)-enantiomer (arketamine). Only esketamine enhances delta power during NREM sleep after gamma activity normalizes, a pattern called the gamma-delta shift. This shift, previously proposed as a marker of antidepressant activity for racemic ketamine, appears specific to esketamine. The findings help clarify which enantiomer drives the EEG changes and suggest that the gamma-delta shift may serve as a biomarker for antidepressant effects, relevant to treatment-resistant depression.