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

作者：Petzer Anel^*; Harvey Brian H; Wegener Gregers; Petzer Jacobus P

来源：Toxicology and Applied Pharmacology, 2012, 258(3): 403-409.

DOI：10.1016/j.taap.2011.12.005

• Methylene blue
• Azure B
• Monoamine oxidase
• Inhibition
• Reversible
• Antidepressant

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.

• 出版日期2012-2-1
• 单位西北大学