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In vitro cannabinoid activity profiling of generic ban-evading brominated synthetic cannabinoid receptor agonists and their analogs.
- Source :
-
Drug testing and analysis [Drug Test Anal] 2024 Jun; Vol. 16 (6), pp. 616-628. Date of Electronic Publication: 2023 Oct 30. - Publication Year :
- 2024
-
Abstract
- Following the enactment of a generic ban in China in 2021, the synthetic cannabinoid market has been evolving, now encompassing even wider structural diversity. Compounds carrying a brominated core such as ADB-5'Br-BUTINACA (ADMB-B-5Br-INACA) and tail-less analogs, such as ADB-5'Br-INACA (ADMB-5Br-INACA), MDMB-5'Br-INACA, and ADB-INACA (ADMB-INACA), have been detected since late 2021. This study investigated the cannabinoid receptor (CB) activation potential of synthesized (S)-enantiomers of these substances, as well as of two predicted analogs MDMB-5'Br-BUTINACA (MDMB-B-5Br-INACA) and ADB-5'F-BUTINACA (ADMB-B-5F-INACA), using CB <subscript>1</subscript> and CB <subscript>2</subscript> β-arrestin 2 recruitment assays and a CB <subscript>1</subscript> intracellular calcium release assay. Surprisingly, the tail-less (S)-ADB-5'Br-INACA and (S)-MDMB-5'Br-INACA retained CB activity, albeit with a decreased potency compared to their tailed counterparts (S)-ADB-5'Br-BUTINACA and (S)-MDMB-5'Br-BUTINACA, respectively, which were potent and efficacious CB <subscript>1</subscript> agonists. Also, at CB <subscript>2</subscript> , tail-less analogs showed a lower potency but increased efficacy. Removing the bromine substitution ((S)-ADB-INACA) resulted in a reduced activity at CB <subscript>1</subscript> ; however, this effect was less prominent at CB <subscript>2</subscript> . Looking at tailed analogs, replacing the bromine with a fluorine substitution ((S)-ADB-5'F-BUTINACA) resulted in an increased potency and efficacy at both receptors. Furthermore, as ADB-5'Br-INACA and MDMB-5'Br-INACA have been frequently detected together in Scottish prisons, this study also evaluated the CB <subscript>1</subscript> receptor activation potential of different mixtures of their respective reference standards, showing no unexpected cannabimimetic effect of combining both substances. Lastly, two powders seized by Belgian Customs and confirmed to contain ADB-5'Br-INACA and MDMB-5'Br-INACA, respectively, were assessed for CB activity. Based on the comparison with their reference standards, varying degrees of purity were suspected.<br /> (© 2023 John Wiley & Sons Ltd.)
- Subjects :
- Humans
Halogenation
Animals
HEK293 Cells
Cricetulus
China
CHO Cells
Cannabinoid Receptor Agonists pharmacology
Cannabinoid Receptor Agonists chemistry
Cannabinoid Receptor Agonists chemical synthesis
Cannabinoids pharmacology
Cannabinoids chemistry
Cannabinoids chemical synthesis
Receptor, Cannabinoid, CB1 agonists
Receptor, Cannabinoid, CB1 metabolism
Receptor, Cannabinoid, CB2 agonists
Receptor, Cannabinoid, CB2 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1942-7611
- Volume :
- 16
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Drug testing and analysis
- Publication Type :
- Academic Journal
- Accession number :
- 37903509
- Full Text :
- https://doi.org/10.1002/dta.3592