BACKGROUND AND PURPOSE: 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. EXPERIMENTAL APPROACH: 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. KEY RESULTS: 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. CONCLUSION AND IMPLICATIONS: 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.

3rd Faculty of Medicine Charles University Prague 10 Czech Republic

CZ OPENSCREEN National Infrastructure for Chemical Biology Department of Informatics and Chemistry Faculty of Chemical Technology University of Chemistry and Technology Prague 6 Czech Republic

CZ OPENSCREEN National Infrastructure for Chemical Biology Institute of Molecular Genetics CAS Prague 4 Czech Republic

Department of Analytical Chemistry University of Chemistry and Technology Prague 6 Czech Republic

Department of Cellular Neurophysiology Institute of Physiology CAS Prague 4 Czech Republic

Department of Experimental Neurobiology National Institute of Mental Health Klecany Czech Republic

Department of Organic Chemistry University of Chemistry and Technology Prague 6 Czech Republic

Forensic Laboratory of Biologically Active Compounds Department of Chemistry of Natural Compounds University of Chemistry and Technology Prague 6 Czech Republic

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Br J Pharmacol. 2022 Jul;179(13):3482. doi: 10.1111/bph.15857. PubMed

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