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Titel: Can a Recently Developed Pig Model Be Used for In Vivo Metabolism Studies of 7-Azaindole-Derived Synthetic Cannabinoids? A Study Using 5F-MDMB-P7AICA
VerfasserIn: Doerr, Adrian A.
Nordmeier, Frederike
Walle, Nadja
Laschke, Matthias W.
Menger, Michael D.
Schmidt, Peter H.
Schaefer, Nadine
Meyer, Markus R.
Sprache: Englisch
Titel: Journal of Analytical Toxicology
Bandnummer: 45 (2021)
Heft: 6
Seiten: 593-604
Verlag/Plattform: Oxford University Press
Erscheinungsjahr: 2020
DDC-Sachgruppe: 610 Medizin, Gesundheit
Dokumenttyp: Journalartikel / Zeitschriftenartikel
Abstract: New psychoactive substances (NPS), especially synthetic cannabinoids (SC) remain a public health concern. Due to ethical reasons, systematic controlled human studies to elucidate their toxicodynamics and/or toxicokinetics are usually not possible. However, such knowledge is necessary, for example, for determination of screening targets and interpretation of clinical and forensic toxicological data. In the present study, the feasibility of the pig model as an alternative for human in vivo metabolism studies of SC was investigated. For this purpose, the metabolic pattern of the SC methyl-2-{[1-(5-fluoropentyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]amino}-3,3- dimethylbutanoate (5F-MDMB-P7AICA) was elucidated in pig urine following inhalative administration (dosage: 200 µg/kg of body weight). The results were compared with human and pig liver microsomal assays and literature. In addition, different incubations with isolated cytochrome-P450 (CYP) monooxygenases were conducted to identify the involved isozymes. In total, nine phase I and three phase II metabolites were identified in pig urine. The most abundant reactions were ester hydrolysis, ester hydrolysis combined with glucuronidation and ester hydrolysis combined with hydroxylation at the tert-butyl moiety. The parent compound was only found up to 1 h after administration in pig urine. The metabolite formed after hydroxylation and glucuronidation was detectable for 2 h, the one formed after ester hydrolyzation and defluorination for 4 h after administration. All other metabolites were detected during the whole sampling time. The most abundant metabolites were also detected using both microsomal incubations and monooxygenase screenings revealed that CYP3A4 catalyzed most reactions. Finally, pig data showed to be in line with published human data. To conclude, the main metabolites recommended in previous studies as urinary targets were confirmed by using pig urine. The used pig model seems therefore to be a suitable alternative for in vivo metabolism studies of 7-azaindole-derived SC.
DOI der Erstveröffentlichung: 10.1093/jat/bkaa122
URL der Erstveröffentlichung: https://doi.org/10.1093/jat/bkaa122
Link zu diesem Datensatz: urn:nbn:de:bsz:291--ds-441350
hdl:20.500.11880/39467
http://dx.doi.org/10.22028/D291-44135
ISSN: 1945-2403
0146-4760
Datum des Eintrags: 24-Jan-2025
Bezeichnung des in Beziehung stehenden Objekts: Supplementary data
In Beziehung stehendes Objekt: https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/jat/45/6/10.1093_jat_bkaa122/2/bkaa122_supp.zip?Expires=1740141133&Signature=IOHSPGeKxah3mz5lETfmPvdJrp-xz6G488B6VyBgtQIWz-gXh-bXz1E-asuQFgpVhjy41RinFLDuPfegl1bWyzyPtAGDIRyMaoMw-3pRoYvSt4bieUk6WTgLzs57T7QtX7by~Ea8gvfV5AEZY9lNMMlEEYad~4Tp3olajOPWhXCor1SYOuzjfqr-5~7o8JKBxJPJJvO1auYmPyJ4yhjhlc5YhnRVGsD~FwfJjxfE3jiXJ0SDtuR0~XhKP-i0OQlDIzz739Zht8rYYYKf-ggXCIrQ6ah~mn9qXAx5Z6-e0Sy8WjyJDVDjXzhrKu7ci5-CFjFvOAVgYbeD0-LdOTZpYw__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA
Fakultät: M - Medizinische Fakultät
Fachrichtung: M - Chirurgie
M - Experimentelle und Klinische Pharmakologie und Toxikologie
M - Rechtsmedizin
Professur: M - Prof. Dr. Michael D. Menger
M - Prof. Dr. Markus Meyer
M - Prof. Dr. Peter Schmidt
Sammlung:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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