Pharmacokinetic, pharmacodynamic, and behavioural studies of deschloroketamine in Wistar rats.
Kristýna Štefková-mazochová, Hynek Danda, Wim Dehaen, Bronislav Jurásek, Klára Šíchová, Nikola Pinterová-Leca, Vladimír Mazoch, Barbora Hrčka Krausová, Bohdan Kysilov, Tereza Smejkalová, Ladislav Vyklický, Michal Kohout, Kateřina Hájková, Daniel Svozil, Rachel R. Horsley, Martin Kuchař, Tomáš Páleníček
British Journal of Pharmacology 2022 DOI: 10.1111/bph.15680 (opens in new tab)
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Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Wistar rats |
| Interventions | Deschloroketamine S-DCK R-DCK |
| Dose | 5, 10, and 30 mg·kg-1 for DCK; 10 mg·kg-1 for S-DCK and R-DCK |
| Topics | Ketamine |
| Keywords | Nmda receptor Deschloroketamine Enantiomers Locomotion Pharmacokinetics Prepulse inhibition |
| Citations | 13 |
| Key findings | Deschloroketamine shows similar behavioral and addictive profiles to ketamine, with a slightly slower pharmacokinetic profile, and its S-enantiomer is more potent at NMDA receptors and in stimulating locomotion. |
Abstract
Deschloroketamine (DCK), a structural analogue of ketamine, has recently emerged on the illicit drug market as a recreational drug with a modestly long duration of action. Despite it being widely used by recreational users, no systematic research on its effects has been performed to date. Pharmacokinetics, acute effects, and addictive potential in a series of behavioural tests in Wistar rats were performed following subcutaneous (s.c.) administration of DCK (5, 10, and 30 mg·kg-1 ) and its enantiomers S-DCK (10 mg·kg-1 ) and R-DCK (10 mg·kg-1 ). Additionally, activity at human N-methyl-d-aspartate (NMDA) receptors was also evaluated. DCK rapidly crossed the blood brain barrier, with maximum brain levels achieved at 30 min and remaining high at 2 h after administration. Its antagonist activity at NMDA receptors is comparable to that of ketamine with S-DCK being more potent. DCK had stimulatory effects on locomotion, induced place preference, and robustly disrupted PPI. Locomotor stimulant effects tended to disappear more quickly than disruptive effects on PPI. S-DCK had more pronounced stimulatory properties than its R-enantiomer. However, the potency in disrupting PPI was comparable in both enantiomers. DCK showed similar behavioural and addictive profiles and pharmacodynamics to ketamine, with S-DCK being in general more active. It has a slightly slower pharmacokinetic profile than ketamine, which is consistent with its reported longer duration of action. These findings have implications and significance for understanding the risks associated with illicit use of DCK.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
Cited by 7
- Pharmacokinetics, systemic toxicity, thermoregulation and acute behavioural effects of 25CN‐NBOMe Addiction Biology August 4, 2022
- A structural spectroscopic study of dissociative anaesthetic methoxphenidine New Journal of Chemistry 2023
- Zebrafish embryo-larval testing reveals differential toxicity of new psychoactive substances. Toxicology Reports June 1, 2025
- The acute effects of methoxphenidine on behaviour and pharmacokinetics profile in animal model. Progress in Neuro-Psychopharmacology and Biological Psychiatry March 20, 2025
- Hexahydrocannabinol: pharmacokinetics, systemic toxicity, and acute behavioral effects in Wistar rats. The International Journal of Neuropsychopharmacology August 1, 2025
and 2 more in the library
Cites 16
- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
- Ketamine – More mechanisms of action than just NMDA blockade Trends in Anaesthesia and Critical Care March 22, 2014
- The effects of ketamine on dopaminergic function: meta-analysis and review of the implications for neuropsychiatric disorders Molecular Psychiatry October 3, 2017
- Comparison of antidepressant and side effects in mice after intranasal administration of (R,S)-ketamine, (R)-ketamine, and (S)-ketamine. Pharmacology, Biochemistry, and Behavior June 1, 2019
- Electroencephalographic Spectral and Coherence Analysis of Ketamine in Rats: Correlation with Behavioral Effects and Pharmacokinetics Neuropsychobiology 2011
and 11 more in the library