Metabolic pathways of 4-bromo-2,5-dimethoxyphenethylamine (2C-B): analysis of phase I metabolism with hepatocytes of six species including human

• Type: Article in International Scientific Journal
• Date: 2005

Authors

Carmo, H (Author) FFUP; Hengstler, JG (Author) Other; de Boer, D (Author) Other; Ringel, M (Author) Other; Remiao, F (Author) FFUP; Carvalho, F (Author) FFUP; Fernandes, E (Author) FFUP; dos Reys, LA (Author) Other; Oesch, F (Author) Other; Bastos, MD (Author) FFUP

Journal

Title: Toxicology

Vol. 206

Pages: 75-89

ISSN: 0300-483X

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 57 Citations

Scopus - 67 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: P-000-522

DOI: 10.1016/j.tox.2004.07.004

Abstract (EN): 4-Bromo-2,5-dimethoyphyenethylamine (2C-B) is a psychoactive drug of abuse that is sold under the street names ''Venus'', ''Bromo'', ''Erox'', ''XTC'' or "Nexus''. Concern has been raised because only little is known abot its toxicity and metabolism in humans. In the present study we incubated 2C-B with human, monkey, dog, rabbit, rat and mouse hepatocytes to identify the metabolites formed and to determine possibe toxic effects as evidenced by an ATP assay. Our data allow construction of the main metabolic pathways of 2C-B. Oxidative deamination results in the 2-(4-bromo-2,5-dimethyoxphenyl)-ethanol (BDMPE) and 4-bromo-2,5-dimethoxyphenylacetic acid (BDMPAA) metabolites. Additionally, 4-bromo-2,5-dimethoxybenzoic acid (BDMBA) can be produced also by oxidative deamination. Further metabolism of BDMPE and BDMPAA may occur by demethylation. Alternatively, the later metabolites can be generated by demethylation of 2C-B followed by oxidative deamination. Two remarkable interspecies differences in metabolism of 2C-B were observed (i) a hitherto unknown metabolite, 4-bromo-2,5-dimethoxyl-phenol (BDMP), was identified after incubation only with mouse hepatocytes; (ii) 2-(4-bromo-2-hydroxy-5-methoxyphenyl)-ethanol (B-2-HMPE) was produced by hepatocytes from human, monkey and rabbit but not by dog, rat and mouse. Comparing the toxic effects of 2C-B between hepatocytes of the six examined species we observed only minor interspecies differences. However, large inter-individual differences in susceptibility of hepatocytes from three human donors were observed.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 15