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

0555872 - FGÚ 2023 RIV GB eng J - Článek v odborném periodiku
Štefková-Mazochová, K. - Danda, H. - Dehaen, W. - Jurásek, B. - Šíchová, K. - Pinterová-Leca, N. - Mazoch, V. - Hrčka Krausová, Barbora - Kysilov, Bohdan - Smejkalová, Tereza - Vyklický ml., Ladislav - Kohout, M. - Hájková, K. - Svozil, Daniel - Horsley, R. R. - Kuchař, M. - Páleníček, T.
Pharmacokinetic, pharmacodynamic, and behavioural studies of deschloroketamine in Wistar rats.
British Journal of Pharmacology. Roč. 179, č. 1 (2022), s. 65-83. ISSN 0007-1188. E-ISSN 1476-5381
Grant CEP: GA ČR(CZ) GA20-17945S; GA MZd(CZ) EF16_025/0007444; GA MŠMT(CZ) LM2018130
Výzkumná infrastruktura: CZ-OPENSCREEN III - 90130
Institucionální podpora: RVO:67985823 ; RVO:68378050
Klíčová slova: deschloroketamine * enantiomers * locomotion * NMDA receptor * pharmacokinetics * pharmacokinetics
Obor OECD: Pharmacology and pharmacy
Impakt faktor: 7.3, rok: 2022
Způsob publikování: Open access
https://doi.org/10.1111/bph.15680

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 center dot kg(-1)) and its enantiomers S-DCK (10 mg center dot kg(-1)) and R-DCK (10 mg center dot 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.
Trvalý link: http://hdl.handle.net/11104/0330327