Azure B, a metabolite of methylene blue, is a high-potency, reversible inhibitor of monoamine oxidase

Toxicol Appl Pharmacol. 2012 Feb 1;258(3):403-9. doi: 10.1016/j.taap.2011.12.005. Epub 2011 Dec 16.


Methylene blue (MB) has been shown to act at multiple cellular and molecular targets and as a result possesses diverse medical applications. Among these is a high potency reversible inhibition of monoamine oxidase A (MAO-A) that may, at least in part, underlie its adverse effects but also its psycho- and neuromodulatory actions. MB is metabolized to yield N-demethylated products of which azure B, the monodemethyl species, is the major metabolite. Similar to MB, azure B also displays a variety of biological activities and may therefore contribute to the pharmacological profile of MB. Based on these observations, the present study examines the interactions of azure B with recombinant human MAO-A and -B. The results show that azure B is a potent MAO-A inhibitor (IC₅₀=11 nM), approximately 6-fold more potent than is MB (IC₅₀=70 nM) under identical conditions. Measurements of the time-dependency of inhibition suggest that the interaction of azure B with MAO-A is reversible. Azure B also reversibly inhibits the MAO-B isozyme with an IC₅₀ value of 968 nM. These results suggest that azure B may be a hitherto under recognized contributor to the pharmacology and toxicology of MB by blocking central and peripheral MAO-A activity and as such needs to be considered during its use in humans and animals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Azure Stains / administration & dosage
  • Azure Stains / pharmacology*
  • Azure Stains / toxicity
  • Humans
  • Inhibitory Concentration 50
  • Methylene Blue / metabolism*
  • Monoamine Oxidase / drug effects*
  • Monoamine Oxidase / metabolism
  • Monoamine Oxidase Inhibitors / administration & dosage
  • Monoamine Oxidase Inhibitors / pharmacology*
  • Monoamine Oxidase Inhibitors / toxicity
  • Time Factors


  • Azure Stains
  • Monoamine Oxidase Inhibitors
  • Azure B
  • Monoamine Oxidase
  • Methylene Blue