Pharmacokinetic Properties of the Novel Synthetic Cannabinoid 5F-APINAC and Its Influence on Metabolites Associated with Neurotransmission in Rabbit Plasma
| Autor: | Alex Brito, Pavel A. Markin, Natalia L. Bochkareva, Alexey Kukharenko, Andrey Anatolievich Nedorubov, Natalia V. Mesonzhnik, Roman M. Kuznetsov, Alexey V Lyundup, Natalia E. Moskaleva, Franco Tagliaro, Ksenia Shestakova, Elizaveta G Appolonova, Svetlana A. Appolonova |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
Pharmaceutical Science 01 natural sciences Article neurotransmitters 03 medical and health sciences chemistry.chemical_compound Pharmacy and materia medica 0302 clinical medicine Kynurenic acid Pharmacokinetics Internal medicine Drug Discovery Aspartic acid Anthranilic acid medicine Xanthurenic acid metabolites 010401 analytical chemistry Tryptophan metabolomics 0104 chemical sciences RS1-441 Endocrinology chemistry 5F-APINAC UPLC-MS/MS Medicine Molecular Medicine synthetic cannabinoids pharmacokinetics 030217 neurology & neurosurgery Kynurenine Quinolinic acid |
| Zdroj: | Pharmaceuticals Volume 14 Issue 7 Pharmaceuticals, Vol 14, Iss 668, p 668 (2021) |
| ISSN: | 1424-8247 |
| DOI: | 10.3390/ph14070668 |
| Popis: | The strong psychoactive effects of synthetic cannabinoids raise the need for the deeper studying of their neurometabolic effects. The pharmacokinetic properties of 5F-APINAC and its influence on metabolomics profiles associated with neurotransmission were investigated in rabbit plasma. Twelve rabbits divided into three groups received 1-mL 5F-APINAC at 0.1, 1 and 2 mg/kg. The intervention groups were compared with the controls. Sampling was performed at nine time points (0–24 h). Ultra-high-performance liquid chromatography–tandem mass spectrometry was used. The pharmacokinetics were dose-dependent (higher curve at a higher dose) with a rapid biotransformation, followed by gradual elimination within 24 h. The tryptophan concentrations abruptly decreased (p < 0.05) in all tested groups, returning to the basal levels after 6 h. 5-hydroxylindole acetic acid increased (p < 0.05) in the controls, but this trend was absent in the treated groups. The aspartic acid concentrations were elevated (p < 0.001) in the treated groups. L-kynurenine was elevated (p < 0.01) in the intervention groups receiving 1 mg/kg to 2 mg/kg. Dose-dependent elevations (p < 0.01) were found for kynurenic acid, xanthurenic acid and quinolinic acid (p < 0.01), whereas the anthranilic acid trends were decreased (p < 0.01). The indole-3-propionic acid and indole-3-carboxaldehyde trends were elevated (p < 0.05), whereas the indole-3-lactic acid trajectories were decreased (p < 0.01) in the intervention groups. 5F-APINAC administration had a rapid biotransformation and gradual elimination. The metabolites related to the kynurenine and serotonergic system/serotonin pathways, aspartic acid innervation system and microbial tryptophan catabolism were altered. |
| Databáze: | OpenAIRE |
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