Methylene blue (MB) is reported to possess diverse pharmacological actions and is attracting increasing attention for the treatment of
neurodegenerative disorders such as
Alzheimer's disease. Among the pharmacological actions of MB, is the significant inhibition of
acetylcholinesterase (AChE) and
butyrylcholinesterase (BuChE). These activities may, at least in part, underlie MB's beneficial effects in
Alzheimer's disease. MB is metabolized to yield N-demethylated products of which
azure B, the monodemethyl metabolite, is the predominant species.
Azure B has been shown to be pharmacologically active and also possesses a variety of
biological actions.
Azure B therefore may contribute to the pharmacological profile of MB. Based on these considerations, the present study investigates the possibility that
azure B may, similar to MB, act as an inhibitor of human AChE and BuChE. The results document that
azure B inhibits AChE and BuChE with IC50 values of 0.486μM and 1.99μM, respectively. The results further show that
azure B inhibits AChE and BuChE reversibly, and that the modes of inhibition are most likely competitive. Although the AChE and BuChE inhibitory activities of
azure B are twofold and fivefold, respectively, less potent than those recorded for MB [IC50(AChE)=0.214μM; IC50(BuChE)=0.389μM] under identical conditions,
azure B may be a contributor to MB's in vivo activation of the
cholinergic system and beneficial effects in
Alzheimer's disease.