In Vitro Characterization of the Pyrazole-Carrying Synthetic Cannabinoid Receptor Agonist 5F-3,5-AB-PFUPPYCA and its Structural Analogs

Introduction: Pyrazole-carrying “FUPPYCA” synthetic cannabinoid receptor agonists (SCRAs) have made short-lived appearances on the market since 2015. However, 5F-3,5-AB-PFUPPYCA and 3,5-ADB-4en-PFUPPYCA have recently been detected in Scottish prisons. This re-emergence is believed to be triggered by...

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Main Authors: M.H. Deventer, C. Norman, R. Reid, C. McKenzie, N.N. Daeid, C.P. Stove
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:Emerging Trends in Drugs, Addictions, and Health
Online Access:http://www.sciencedirect.com/science/article/pii/S2667118223000375
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author M.H. Deventer
C. Norman
R. Reid
C. McKenzie
N.N. Daeid
C.P. Stove
author_facet M.H. Deventer
C. Norman
R. Reid
C. McKenzie
N.N. Daeid
C.P. Stove
author_sort M.H. Deventer
collection DOAJ
description Introduction: Pyrazole-carrying “FUPPYCA” synthetic cannabinoid receptor agonists (SCRAs) have made short-lived appearances on the market since 2015. However, 5F-3,5-AB-PFUPPYCA and 3,5-ADB-4en-PFUPPYCA have recently been detected in Scottish prisons. This re-emergence is believed to be triggered by the Chinese generic SCRA ban (2021). Methods: Infused paper samples, seized from different Scottish prisons were analyzed to assess the prevalence of FUPPYCA SCRAs. Six structurally related analogs were then functionally characterized using live cell receptor-based assays, based on the functional complementation of a nanoluciferase enzyme. Results: 5F-3,5-AB-PFUPPYCA and 3,5-ADB-4en-PFUPPYCA mixtures were detected 9 times in Scottish prisons since July 2021. Most FUPPYCA SCRAs were found to be inactive at both CB1 and CB2, with only 3 analogs showing some (minor) CB1 activation potential (3,5-AB-CHMFUPPYCA, 5,3-AB-CHMFUPPYCA and 5,3-ADB-4en-PFUPPYCA). Interestingly, the 5,3 regioisomers (covered by the ban) were more active than their 3,5 counterparts. Furthermore, all analogs had antagonistic properties, potentially related to their structural resemblance to cannabinoid antagonists. Conclusions: Given their weak CB activity, FUPPYCA SCRAs are not expected to pose a serious health hazard, despite their ability to evade the generic ban. This may also explain their only transient re-emergence in Scottish prisons.
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spelling doaj-art-8f5f96c2f63945ee9c35cd9776c58b3d2024-12-14T06:33:36ZengElsevierEmerging Trends in Drugs, Addictions, and Health2667-11822024-12-014100086In Vitro Characterization of the Pyrazole-Carrying Synthetic Cannabinoid Receptor Agonist 5F-3,5-AB-PFUPPYCA and its Structural AnalogsM.H. Deventer0C. Norman1R. Reid2C. McKenzie3N.N. Daeid4C.P. Stove5Ghent University, BelgiumGhent University, BelgiumGhent University, BelgiumGhent University, BelgiumGhent University, BelgiumGhent University, BelgiumIntroduction: Pyrazole-carrying “FUPPYCA” synthetic cannabinoid receptor agonists (SCRAs) have made short-lived appearances on the market since 2015. However, 5F-3,5-AB-PFUPPYCA and 3,5-ADB-4en-PFUPPYCA have recently been detected in Scottish prisons. This re-emergence is believed to be triggered by the Chinese generic SCRA ban (2021). Methods: Infused paper samples, seized from different Scottish prisons were analyzed to assess the prevalence of FUPPYCA SCRAs. Six structurally related analogs were then functionally characterized using live cell receptor-based assays, based on the functional complementation of a nanoluciferase enzyme. Results: 5F-3,5-AB-PFUPPYCA and 3,5-ADB-4en-PFUPPYCA mixtures were detected 9 times in Scottish prisons since July 2021. Most FUPPYCA SCRAs were found to be inactive at both CB1 and CB2, with only 3 analogs showing some (minor) CB1 activation potential (3,5-AB-CHMFUPPYCA, 5,3-AB-CHMFUPPYCA and 5,3-ADB-4en-PFUPPYCA). Interestingly, the 5,3 regioisomers (covered by the ban) were more active than their 3,5 counterparts. Furthermore, all analogs had antagonistic properties, potentially related to their structural resemblance to cannabinoid antagonists. Conclusions: Given their weak CB activity, FUPPYCA SCRAs are not expected to pose a serious health hazard, despite their ability to evade the generic ban. This may also explain their only transient re-emergence in Scottish prisons.http://www.sciencedirect.com/science/article/pii/S2667118223000375
spellingShingle M.H. Deventer
C. Norman
R. Reid
C. McKenzie
N.N. Daeid
C.P. Stove
In Vitro Characterization of the Pyrazole-Carrying Synthetic Cannabinoid Receptor Agonist 5F-3,5-AB-PFUPPYCA and its Structural Analogs
Emerging Trends in Drugs, Addictions, and Health
title In Vitro Characterization of the Pyrazole-Carrying Synthetic Cannabinoid Receptor Agonist 5F-3,5-AB-PFUPPYCA and its Structural Analogs
title_full In Vitro Characterization of the Pyrazole-Carrying Synthetic Cannabinoid Receptor Agonist 5F-3,5-AB-PFUPPYCA and its Structural Analogs
title_fullStr In Vitro Characterization of the Pyrazole-Carrying Synthetic Cannabinoid Receptor Agonist 5F-3,5-AB-PFUPPYCA and its Structural Analogs
title_full_unstemmed In Vitro Characterization of the Pyrazole-Carrying Synthetic Cannabinoid Receptor Agonist 5F-3,5-AB-PFUPPYCA and its Structural Analogs
title_short In Vitro Characterization of the Pyrazole-Carrying Synthetic Cannabinoid Receptor Agonist 5F-3,5-AB-PFUPPYCA and its Structural Analogs
title_sort in vitro characterization of the pyrazole carrying synthetic cannabinoid receptor agonist 5f 3 5 ab pfuppyca and its structural analogs
url http://www.sciencedirect.com/science/article/pii/S2667118223000375
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