In vitro phase I metabolism of three phenethylamines 25D-NBOMe, 25E-NBOMe and 25N-NBOMe using microsomal and microbial models.

Grafinger, Katharina Elisabeth; Stahl, Katja; Wilke, Andreas; König, Stefan; Weinmann, Wolfgang (2018). In vitro phase I metabolism of three phenethylamines 25D-NBOMe, 25E-NBOMe and 25N-NBOMe using microsomal and microbial models. Drug testing and analysis, 10(10), pp. 1607-1626. Wiley 10.1002/dta.2446

[img]
Preview
Text
Grafinger_et_al-2018-Drug_Testing_and_Analysis.pdf - Accepted Version
Available under License Publisher holds Copyright.

Download (3MB) | Preview

Numerous 2,5-dimethoxy-N-benzylphenethylamines (NBOMe), carrying a variety of lipophilic substituents at the 4-position, are potent agonists at 5-hydroxytryptamine (5HT ) receptors and show hallucinogenic effects. The present study investigated the metabolism of 25D-NBOMe, 25E-NBOMe and 25N-NBOMe using the microsomal model of pooled human liver microsomes (pHLM) and the microbial model of the fungi Cunninghamella elegans (C. elegans). Identification of metabolites was performed using liquid chromatography-high resolution-tandem mass spectrometry (LC-HR-MS/MS) with a QqToF instrument. In total, 36 25D-NBOMe phase I metabolites, 26 25E-NBOMe phase I metabolites and 24 25N-NBOMe phase I metabolites were detected and identified in pHLM. Furthermore, 14 metabolites of 25D-NBOMe, eleven 25E-NBOMe metabolites and nine 25N-NBOMe metabolites could be found in C. elegans. The main biotransformation steps observed were oxidative deamination, oxidative N-dealkylation also in combination with hydroxylation, oxidative O-demethylation possibly combined with hydroxylation, oxidation of secondary alcohols, mono- and dihydroxylation, oxidation of primary alcohols and carboxylation of primary alcohols. Additionally, oxidative di-O-demethylation for 25E-NBOMe and reduction of the aromatic nitro group and N-acetylation of the primary aromatic amine for 25N-NBOMe took place. The resulting 25N-NBOMe metabolites were unique for NBOMe compounds. For all NBOMes investigated, the corresponding 2,5-dimethoxyphenethylamine (2C-X) metabolite was detected. This study reports for the first time 25X-NBOMe N-oxide metabolites and hydroxylamine metabolites, which were identified for 25D-NBOMe and 25N-NBOMe and all three investigated NBOMes, respectively. C. elegans was capable of generating all main biotransformation steps observed in pHLM and might therefore be an interesting model for further studies of new psychoactive substances (NPS) metabolism.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Legal Medicine
04 Faculty of Medicine > Service Sector > Institute of Legal Medicine > Forensic Chemistry and Toxicology
04 Faculty of Medicine > Service Sector > Institute of Legal Medicine > Management

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

König, Stefan and Weinmann, Wolfgang

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1942-7603

Publisher:

Wiley

Language:

English

Submitter:

Antoinette Angehrn

Date Deposited:

10 Jul 2018 09:59

Last Modified:

25 Oct 2019 00:44

Publisher DOI:

10.1002/dta.2446

PubMed ID:

29971945

Uncontrolled Keywords:

Metabolism NBOMe NPS fungi Cunninghamella elegans pHLM

BORIS DOI:

10.7892/boris.118481

URI:

https://boris.unibe.ch/id/eprint/118481

Actions (login required)

Edit item Edit item
Provide Feedback