Drug Administration Routes Impact the Metabolism of a Synthetic Cannabinoid in the Zebrafish Larvae Model.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
MetadataShow full item record
AbstractZebrafish (Danio rerio) larvae have gained attention as a valid model to study in vivo drug metabolism and to predict human metabolism. The microinjection of compounds, oligonucleotides, or pathogens into zebrafish embryos at an early developmental stage is a well-established technique. Here, we investigated the metabolism of zebrafish larvae after microinjection of methyl 2-(1-(5-fluoropentyl)-1H-pyrrolo[2,3-b]pyridine-3-carboxamido)-3,3-dimethylbutanoate (7'N-5F-ADB) as a representative of recently introduced synthetic cannabinoids. Results were compared to human urine data and data from the in vitro HepaRG model and the metabolic pathway of 7'N-5F-ADB were reconstructed. Out of 27 metabolites detected in human urine samples, 19 and 15 metabolites were present in zebrafish larvae and HepaRG cells, respectively. The route of administration to zebrafish larvae had a major impact and we found a high number of metabolites when 7'N-5F-ADB was microinjected into the caudal vein, heart ventricle, or hindbrain. We further studied the spatial distribution of the parent compound and its metabolites by mass spectrometry imaging (MSI) of treated zebrafish larvae to demonstrate the discrepancy in metabolite profiles among larvae exposed through different administration routes. In conclusion, zebrafish larvae represent a superb model for studying drug metabolism, and when combined with MSI, the optimal administration route can be determined based on in vivo drug distribution.
CitationMolecules. 2020 Sep 29;25(19):E4474. doi: 10.3390/molecules25194474.
AffiliationHIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.
JournalMolecules (Basel, Switzerland)
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-ShareAlike 4.0 International
- Metabolic fate of the new synthetic cannabinoid 7'N-5F-ADB in rat, human, and pooled human S9 studied by means of hyphenated high-resolution mass spectrometry.
- Authors: Richter LHJ, Maurer HH, Meyer MR
- Issue date: 2019 Feb
- Tools for studying the metabolism of new psychoactive substances for toxicological screening purposes - A comparative study using pooled human liver S9, HepaRG cells, and zebrafish larvae.
- Authors: Richter LHJ, Herrmann J, Andreas A, Park YM, Wagmann L, Flockerzi V, Müller R, Meyer MR
- Issue date: 2019 May 1
- Metabolic profiling of synthetic cannabinoid 5F-ADB by human liver microsome incubations and urine samples using high-resolution mass spectrometry.
- Authors: Yeter O, Ozturk YE
- Issue date: 2019 Jun
- Metabolic profiling of synthetic cannabinoid 5F-ADB and identification of metabolites in authentic human blood samples via human liver microsome incubation and ultra-high-performance liquid chromatography/high-resolution mass spectrometry.
- Authors: Presley BC, Castaneto MS, Logan BK, Jansen-Varnum SA
- Issue date: 2020 Nov 30
- Distinguishing Intake of New Synthetic Cannabinoids ADB-PINACA and 5F-ADB-PINACA with Human Hepatocyte Metabolites and High-Resolution Mass Spectrometry.
- Authors: Carlier J, Diao X, Scheidweiler KB, Huestis MA
- Issue date: 2017 May