title: Azure B, a metabolite of methylene blue, is a high-potency, reversible inhibitor of monoamine oxidase.
abstract: 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.
authors.affiliation: Unit for Drug Research and Development, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa. 12264954@nwu.ac.za
authors.forename: Anél
authors.initials: A
authors.lastname: Petzer
authors.forename: Brian H
authors.initials: BH
authors.lastname: Harvey
authors.forename: Gregers
authors.initials: G
authors.lastname: Wegener
authors.forename: Jacobus P
authors.initials: JP
authors.lastname: Petzer
mesh_terms: D001399:Azure Stains / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D006801:Humans; D020128:Inhibitory Concentration 50; D008751:Methylene Blue / Q000378:metabolism*; D008995:Monoamine Oxidase / Q000187:drug effects* / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D013997:Time Factors
chemical_list: D001399:Azure Stains; D008996:Monoamine Oxidase Inhibitors; C025819:Azure B; D008995:Monoamine Oxidase; D008751:Methylene Blue