In vivo metabolism of the new synthetic cannabinoid APINAC in rats by GC–MS and LC–QTOF-MS

Savchuk, S. A.; Appolonova, Svetlana A.; Pechnikov, Alexander; Rizvanova, L. N.; Shestakova, Ksenia; Tagliaro, Franco

doi:10.1007/s11419-017-0364-y

Cited by 15 publications

(9 citation statements)

References 14 publications

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“…As nothing with these chemical characteristics has previously been reported, EIMS was unable to distinguish which indazole/azaindole ring system was present in the sample. Detection of this compound was subsequently reported in South Korea in 2016 and Russia in 2017 [26,27].…”

Section: Introductionmentioning

confidence: 92%

New-generation azaindole-adamantyl-derived synthetic cannabinoids

et al. 2019

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Purpose This work reports the synthesis and pharmacological and analytical data for a new series of recently identified azaindole-adamantyl-derived synthetic cannabinoids (SCs). Methods Each SC was synthesised using an efficient and divergent synthesis, and assessed by electron ionisation mass spectrometry (EIMS). The cannabimimetic activity of each compound was conducted using a fluorometric imaging plate reader (FLIPR) assay. Results The described EIMS method and retention time by gas chromatography were able to effectively differentiate each of the analogues regardless of the bicyclic core. For the first time in these SC structures, the bicyclic ring system was shown to have an impact on the cannabimimetic activities in the fluorometric assay of membrane potential. Analogues ranged from moderately potent at both CB 1 and CB 2 (e.g., AP4AIC EC 50 = 160 nM and EC 50 = 64 nM, respectively) to not active at either cannabinoid receptor (AP4AICA, AP5AICA, and APIC). Conclusions Further investigation into receptor selectivity surrounding these bicyclic cores could prove useful for future therapeutic applications. Keywords Synthetic cannabinoid • Azaindole • Adamantyl • CB 1 and CB 2 • APICA • Gas chromatography-mass spectrometry Electronic supplementary material The online version of this article (

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Section: Introductionmentioning

confidence: 92%

New-generation azaindole-adamantyl-derived synthetic cannabinoids

et al. 2019

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“…To circumvent this problem, different strategies can be used. In the in vivo approach, healthy animals (typically mice or rats) are exposed to the compound of interest, and blood and urine samples are usually collected to elucidate the metabolites. Nevertheless, it is possible that some metabolites obtained with an animal model are not found in humans, or the major metabolites identified in humans are not the major ones in other species.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive investigation on synthetic cannabinoids: Metabolic behavior and potency testing, using 5F‐APP‐PICA and AMB‐FUBINACA as model compounds

Fabregat‐Safont

Mardal

Noble

et al. 2019

Drug Testing and Analysis

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Synthetic cannabinoids (SCs) represented 45% of new psychoactive substances seizures in Europe (data from 2016). The consumption of SCs is an issue of concern due to their still unknown toxicity and effects on human health, the great variety of compounds synthetized, and the continuous modifications being made to their chemical structure to avoid regulatory issues. These compounds are extensively metabolized in the organism and often cannot be detected as the intact molecule in human urine. The monitoring of SCs in forensic samples must be performed by the analysis of their metabolites. In this work, a workflow for the comprehensive study of SC consumption is proposed and applied to 5F‐APP‐PICA (also known as PX 1 or SRF‐30) and AMB‐FUBINACA (also known as FUB‐AMB or MMB‐FUBINACA), based not only on the elucidation of their metabolites but also including functional data using the NanoLuc approach, previously published. Both cannabinoids were completely metabolized by human hepatocytes (12 and 8 metabolites were elucidated by high resolution mass spectrometry for 5F‐APP‐PICA and AMB‐FUBINACA, respectively) and therefore suitable consumption markers are proposed. The bioassays revealed that 5F‐APP‐PICA presented lower activity than AMB‐FUBINACA at CB1 and CB2 receptors, based on the half maximal effective concentration (EC50) and the maximum response (Emax). These results are in agreement with the different intoxication cases found in the literature for AMB‐FUBINACA.

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“… Compound Study approach Ref. 3,5-AB-CHMFUPPYCA Pooled human liver microsomes (pHLM) [ 351 ] ADB-FUBINACA Authentic human urine [ 352 ] ADB-FUBINACA HLM [ 353 ] 4′N–5F-ADB Rat and human urine, pooled human S9 [ 354 ] AM-694 Human urine (clinical casework) [ 355 ] AM-2201 Human urine (clinical casework) [ 355 ] AMB-CHMICA Pooled rat and human hepatocytes [ 356 ] APINAC (AKB-57, ACBL(N)-018) Rat urine samples Rat liver microsomes and blood sample of rats administered [ 357 ] [ 358 ] BB-22 Urine and/or serum specimens Human hepatocytes [ 359 ] [ 360 ] 5F-ADB HLM [ 361 ] 5C-AKB48 Pooled human hepatocytes and rat Hepatocytes [ 356 ] CUMYL-PICA Rat and HLM [ 362 ] CUMYL-PINACA pHLM pHLM and huma...…”

Section: Challenges – Selected Topic Of Forensic Interestsmentioning

confidence: 99%