Bromo-dragonfly, a psychoactive benzodifuran, is resistant to hepatic metabolism and potently inhibits monoamine oxidase A

Toxicol Lett. 2018 Oct 1;295:397-407. doi: 10.1016/j.toxlet.2018.07.018. Epub 2018 Jul 20.


Bromo-dragonfly is a benzodifuran derivative known as one of the most potent 5-HT2A-receptor agonists within this chemical class, with long-lasting effects of up to 2-3 days. In addition to hallucinogenic effects, the drug is a potent vasoconstrictor, resulting in severe adverse effects, such as necrosis of the limbs. In some cases, intoxication has had fatal outcomes. Little is known about the metabolism of bromo-dragonfly. The aims of this study were to investigate the pharmacokinetics of bromo-dragonfly, determine the plasma protein binding, examine the human hepatic metabolism in vitro, and compare with those of its close analogue, 2C-B-fly. Additionally, we assayed the inhibition potency of both compounds on the monoamine oxidase (MAO) A- and B-mediated oxidative deamination of serotonin (5-HT) and dopamine, respectively. Liquid chromatography high-resolution mass spectrometry was used for metabolism studies in pooled human liver microsomes (HLM), pooled human liver cytosol (HLC) and recombinant enzymes. Inhibition studies of the deamination of 5-HT and dopamine were carried out using LC-MS/MS. Bromo-dragonfly was not metabolised in the tested in vitro systems. On the other hand, 2C-B-fly was metabolised in HLM by CYP2D6 and in HLC to some extent, with the main biotransformations being monohydroxylation and N-acetylation. Furthermore, MAO-A metabolised 2C-B-fly, producing the aldehyde metabolite, which was trapped in vitro with methoxyamine. Inhibition experiments revealed that bromo-dragonfly is a competitive inhibitor of MAO-A with a Ki of 0.352 μM. The IC50 value for bromo-dragonfly indicated that the inhibition of MAO-A may be clinically relevant. However, more data are needed to estimate its impact on the increase of 5-HT in vivo.

Keywords: Benzodifuran; High-resolution mass spectrometry; Inhibition; Metabolism; Monoamine oxidase; Protein binding.

Publication types

  • Comparative Study

MeSH terms

  • Acetylation
  • Biotransformation
  • Bromobenzoates / metabolism*
  • Bromobenzoates / pharmacology*
  • Chromatography, High Pressure Liquid
  • Cytochrome P-450 CYP2D6 / metabolism
  • Deamination
  • Dopamine / metabolism
  • Hallucinogens / metabolism*
  • Hallucinogens / pharmacology*
  • Humans
  • Hydroxylation
  • Kinetics
  • Microsomes, Liver / enzymology*
  • Monoamine Oxidase / metabolism*
  • Monoamine Oxidase Inhibitors / metabolism*
  • Monoamine Oxidase Inhibitors / pharmacology*
  • Oxidation-Reduction
  • Propylamines / metabolism*
  • Propylamines / pharmacology*
  • Protein Binding
  • Serotonin / metabolism
  • Tandem Mass Spectrometry


  • 1-(8-bromobenzo(1,2-b;4,5-b')difuran-4-yl)-2-aminopropane
  • Bromobenzoates
  • Hallucinogens
  • Monoamine Oxidase Inhibitors
  • Propylamines
  • Serotonin
  • Cytochrome P-450 CYP2D6
  • Monoamine Oxidase
  • monoamine oxidase A, human
  • Dopamine