Monti, Manuela Carla and Scheurer, Eva and Mercer-Chalmers-Bender, Katja. (2021) Phase I In Vitro Metabolic Profiling of the Synthetic Cannabinoid Receptor Agonists CUMYL-THPINACA and ADAMANTYL-THPINACA. Metabolites, 11 (8). p. 470.
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Abstract
Synthetic cannabinoid receptor agonists (SCRAs) remain popular drugs of abuse. As many SCRAs are known to be mostly metabolized, in vitro phase I metabolic profiling was conducted of the two indazole-3-carboxamide SCRAs: CUMYL-THPINACA and ADAMANTYL-THPINACA. Both compounds were incubated using pooled human liver microsomes. The sample clean-up consisted of solid phase extraction, followed by analysis using liquid chromatography coupled to a high resolution mass spectrometer. In silico-assisted metabolite identification and structure elucidation with the data-mining software Compound Discoverer was applied. Overall, 28 metabolites were detected for CUMYL-THPINACA and 13 metabolites for ADAMATYL-THPINACA. Various mono-, di-, and tri-hydroxylated metabolites were detected. For each SCRA, an abundant and characteristic di-hydroxylated metabolite was identified as a possible in vivo biomarker for screening methods. Metabolizing cytochrome P450 isoenzymes were investigated via incubation of relevant recombinant liver enzymes. The involvement of mainly CYP3A4 and CYP3A5 in the metabolism of both substances were noted, and for CUMYL-THPINACA the additional involvement (to a lesser extent) of CYP2C8, CYP2C9, and CYP2C19 was observed. The results suggest that ADAMANTYL-THPINACA might be more prone to metabolic drug−drug interactions than CUMYL-THPINACA, when co-administrated with strong CYP3A4 inhibitors.
Faculties and Departments: | 03 Faculty of Medicine 03 Faculty of Medicine > Departement Biomedical Engineering 03 Faculty of Medicine > Departement Biomedical Engineering > Imaging and Computational Modelling > Forensic Medicine (Scheurer) |
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UniBasel Contributors: | Monti, Manuela Carla and Scheurer, Eva and Mercer-Chalmers-Bender, Katja |
Item Type: | Article, refereed |
Article Subtype: | Research Article |
Publisher: | MDPI |
e-ISSN: | 2218-1989 |
Note: | Publication type according to Uni Basel Research Database: Journal article |
Language: | English |
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Last Modified: | 26 Aug 2021 14:03 |
Deposited On: | 26 Aug 2021 14:03 |
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