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Metabolic pathways of 4-bromo-2,5-dimethoxyphenethylamine (2C-B): analysis of phase I metabolism with hepatocytes of six species including human.
Carmo, Helena; Hengstler, Jan G; de Boer, Douwe; Ringel, Michael; Remião, Fernando; Carvalho, Félix; Fernandes, Eduarda; dos Reys, Lesseps A; Oesch, Franz; de Lourdes Bastos, Maria.
Afiliación
  • Carmo H; REQUIMTE, Toxicology Department, Faculty of Pharmacy, University of Porto, Rua Aníbal Cunha 164, 4050-047 Porto, Portugal. helenacarmo@ff.up.pt
Toxicology ; 206(1): 75-89, 2005 Jan 05.
Article en En | MEDLINE | ID: mdl-15590110
4-Bromo-2,5-dimethoxyphenethylamine (2C-B) is a psychoactive designer 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 about 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 possible 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-dimethoxyphenyl)-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-dimethoxy-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.
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Drogas Ilícitas / Hepatocitos / 2,5-Dimetoxi-4-Metilanfetamina Límite: Animals / Humans / Male / Middle aged Idioma: En Revista: Toxicology Año: 2005 Tipo del documento: Article País de afiliación: Portugal Pais de publicación: Irlanda
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Drogas Ilícitas / Hepatocitos / 2,5-Dimetoxi-4-Metilanfetamina Límite: Animals / Humans / Male / Middle aged Idioma: En Revista: Toxicology Año: 2005 Tipo del documento: Article País de afiliación: Portugal Pais de publicación: Irlanda