In-depth comparison of the metabolic and pharmacokinetic behaviour of the structurally related synthetic cannabinoids AMB-FUBINACA and AMB-CHMICA in rats
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In-depth comparison of the metabolic and pharmacokinetic behaviour of the structurally related synthetic cannabinoids AMB-FUBINACA and AMB-CHMICA in rats. / Fabregat-Safont, David; Mata-Pesquera, María; Barneo-Muñoz, Manuela; Martinez-Garcia, Ferran; Mardal, Marie; Davidsen, Anders B.; Sancho, Juan V.; Hernández, Félix; Ibáñez, María.
I: Communications Biology , Bind 5, Nr. 1, 161, 2022.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - In-depth comparison of the metabolic and pharmacokinetic behaviour of the structurally related synthetic cannabinoids AMB-FUBINACA and AMB-CHMICA in rats
AU - Fabregat-Safont, David
AU - Mata-Pesquera, María
AU - Barneo-Muñoz, Manuela
AU - Martinez-Garcia, Ferran
AU - Mardal, Marie
AU - Davidsen, Anders B.
AU - Sancho, Juan V.
AU - Hernández, Félix
AU - Ibáñez, María
N1 - Funding Information: D. Fabregat-Safont, J.V. Sancho, F. Hern?ndez and M. Ib??ez acknowledge financial support from the Generalitat Valenciana (PROMETEO/2019/040) and the University Jaume I (UJI-B2018-19). D. Fabregat-Safont acknowledges Ministerio de Educaci?n, Cultura y Deporte in Spain for his predoctoral grant (FPU15/02033). M. Mata-Pesquera acknowledges Ministerio de Educaci?n y Formaci?n Profesional in Spain for her undergraduate research grant (998142). F. Martinez-Garcia and M. Barneo-Mu?oz acknowledge financial support from Ministerio de Econom?a y Competitividad-FEDER (BFU2016-77691-C2-1-P) and the Generalitat Valenciana (PROMETEO/2016/076). Funding Information: D. Fabregat-Safont, J.V. Sancho, F. Hernández and M. Ibáñez acknowledge financial support from the Generalitat Valenciana (PROMETEO/2019/040) and the University Jaume I (UJI-B2018-19). D. Fabregat-Safont acknowledges Ministerio de Educación, Cultura y Deporte in Spain for his predoctoral grant (FPU15/02033). M. Mata-Pesquera acknowledges Ministerio de Educación y Formación Profesional in Spain for her undergraduate research grant (998142). F. Martinez-Garcia and M. Barneo-Muñoz acknowledge financial support from Ministerio de Economía y Competitividad-FEDER (BFU2016-77691-C2-1-P) and the Generalitat Valenciana (PROMETEO/2016/076).
PY - 2022
Y1 - 2022
N2 - Synthetic cannabinoids receptor agonists (SCRAs) are often almost completely metabolised, and hence their pharmacokinetics should be carefully evaluated for determining the most adequate biomarker in toxicological analysis. Two structurally related SCRAs, AMB-FUBINACA and AMB-CHMICA, were selected to evaluate their in vivo metabolism and pharmacokinetics using male Sprague-Dawley rats. Brain, liver, kidney, blood (serum) and urine samples were collected at different times to assess the differences in metabolism, metabolic reactions, tissue distribution and excretion. Both compounds experimented O-demethyl reaction, which occurred more rapidly for AMB-FUBINACA. The parent compounds and O-demethyl metabolites were highly bioaccumulated in liver, and were still detected in this tissue 48 h after injection. The different indazole/indole N-functionalisation produced diverse metabolic reactions in this moiety and thus, different urinary metabolites were formed. Out of the two compounds, AMB-FUBINACA seemed to easily cross the blood-brain barrier, presenting higher brain/serum concentrations ratio than AMB-CHMICA.
AB - Synthetic cannabinoids receptor agonists (SCRAs) are often almost completely metabolised, and hence their pharmacokinetics should be carefully evaluated for determining the most adequate biomarker in toxicological analysis. Two structurally related SCRAs, AMB-FUBINACA and AMB-CHMICA, were selected to evaluate their in vivo metabolism and pharmacokinetics using male Sprague-Dawley rats. Brain, liver, kidney, blood (serum) and urine samples were collected at different times to assess the differences in metabolism, metabolic reactions, tissue distribution and excretion. Both compounds experimented O-demethyl reaction, which occurred more rapidly for AMB-FUBINACA. The parent compounds and O-demethyl metabolites were highly bioaccumulated in liver, and were still detected in this tissue 48 h after injection. The different indazole/indole N-functionalisation produced diverse metabolic reactions in this moiety and thus, different urinary metabolites were formed. Out of the two compounds, AMB-FUBINACA seemed to easily cross the blood-brain barrier, presenting higher brain/serum concentrations ratio than AMB-CHMICA.
U2 - 10.1038/s42003-022-03113-5
DO - 10.1038/s42003-022-03113-5
M3 - Journal article
C2 - 35210552
AN - SCOPUS:85125359844
VL - 5
JO - Communications Biology
JF - Communications Biology
SN - 2399-3642
IS - 1
M1 - 161
ER -
ID: 299485217