Pharmacokinetic, pharmacodynamic, and behavioural studies of deschloroketamine (DCK) in Wistar rats.

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) and its enantiomers S-DCK (10 mg/kg) and R-DCK (10 mg/kg). Additionally, activity at human N-methyl-d-aspartate (NMDA) receptors was also evaluated. KEY RESULTS DCK rapidly crosses the blood brain barrier, with maximum brain levels achieved at 30 min and remaining high at 2 hrs after administration. Its antagonist activity at NMDA receptors is comparable to the 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 counterpart. However, the potency in disrupting PPI was comparable in both enantiomers. CONCLUSION AND IMPLICATIONS DCK shows 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. The findings have implications and significance for understanding the risks associated with the illicit use of DCK.