Pharmacokinetic, pharmacodynamic, and behavioural studies of deschloroketamine in Wistar rats

Abstract

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 mgÁkg À1 ) and its enantiomers S-DCK (10 mgÁkg À1 ) and R-DCK (10 mgÁkg À1 ). Additionally, activity at human N-methyl-Daspartate (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.

Pharmacokinetics, systemic toxicity, thermoregulation and acute behavioural effects of 25CN‐NBOMe

“…The following parameters were measured: trajectory length divided into 5‐min intervals (centimetre; corrected for deviations of < 3 cm), time spent in the central zone (seconds; T centre = ∑ time central zones ) and probability of occurrence in the peripheral zone (thigmotaxis = Σ f peripheral zones /Σ f all zones , where f = frequency of occurrence in a zone). The described procedure is consistent with our previous studies 17–20 …”

“…A series of experiments intending to describe the effects of psychoactive substances were used 17–22 . The drug's brain and serum levels were examined over 24 h according to the long‐term effect reported by recreational NBOMes users 1 .…”

“…A series of experiments intending to describe the effects of psychoactive substances were used. [17][18][19][20][21][22] The drug's brain and serum levels were examined over 24 h according to the long-term effect reported by recreational NBOMes users. 1 Because of poor oral bioavailability, the relevant doses were administered subcutaneously (s.c.) as a surrogate for standard oral administration in toxicity assay 423 defined by Organisation for Economic Co-operation and Development (OECD).…”

A structural spectroscopic study of dissociative anaesthetic methoxphenidine

“…29 This is true also for dissociative anaesthetics and, particularly, ketamine; 2 the enantiomerically pure metabolites are being screened because of their high pharmaceutical potential. 30 The resolution and characterization of enantiomers of NPS are therefore of eminent interest not only due to toxicity differences but also due to their pharmaceutical potential.…”