Metabolic Pathways of 4-bromo-2,5-dimethoxyphenethylamine (2C-B): Analysis of Phase I Metabolism With Hepatocytes of Six Species Including Human

Toxicology. 2005 Jan 5;206(1):75-89. doi: 10.1016/j.tox.2004.07.004.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2,5-Dimethoxy-4-Methylamphetamine / analogs & derivatives*
  • 2,5-Dimethoxy-4-Methylamphetamine / chemistry
  • 2,5-Dimethoxy-4-Methylamphetamine / metabolism*
  • 2,5-Dimethoxy-4-Methylamphetamine / toxicity
  • Adenosine Triphosphate / metabolism
  • Animals
  • Cells, Cultured
  • Deamination
  • Dogs
  • Dose-Response Relationship, Drug
  • Gas Chromatography-Mass Spectrometry
  • Hepatocytes / metabolism*
  • Humans
  • Illicit Drugs / metabolism*
  • Macaca fascicularis
  • Male
  • Mice
  • Mice, Inbred Strains
  • Middle Aged
  • Molecular Structure
  • Oxidation-Reduction
  • Rabbits
  • Rats
  • Rats, Sprague-Dawley
  • Species Specificity

Substances

  • Illicit Drugs
  • 2,5-Dimethoxy-4-Methylamphetamine
  • 2,5-dimethoxy-4-bromoamphetamine
  • Adenosine Triphosphate