Pharmacokinetic, pharmacodynamic, and behavioural studies of deschloroketamine in Wistar rats.
British journal of pharmacology – January 01, 2022
Source: PubMed
Summary
Deschloroketamine, a recreational drug, rapidly enters the brain, reaching peak levels in just 30 minutes and remaining high for 2 hours. Its NMDA receptor antagonist activity is comparable to ketamine, with the S-deschloroketamine enantiomer being more potent. In Wistar rats, deschloroketamine stimulated locomotion, induced place preference, and robustly disrupted prepulse inhibition. Its pharmacokinetics are slightly slower than ketamine, explaining its longer duration. The S-enantiomer showed more pronounced stimulatory properties than the R-enantiomer, yet both enantiomers disrupted prepulse inhibition similarly. This profile mirrors ketamine's, highlighting risks.
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.