title: The interactions of azure B, a metabolite of methylene blue, with acetylcholinesterase and butyrylcholinesterase.
abstract: 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.
authors.affiliation: Centre of Excellence for Pharmaceutical Sciences, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa. Electronic address: 12264954@nwu.ac.za.
authors.forename: Anél
authors.initials: A
authors.lastname: Petzer
authors.affiliation: Centre of Excellence for Pharmaceutical Sciences, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa.
authors.forename: Brian H
authors.initials: BH
authors.lastname: Harvey
authors.affiliation: Division of Pharmaceutical Chemistry, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa.
authors.forename: Jacobus P
authors.initials: JP
authors.lastname: Petzer
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000544:Alzheimer Disease / Q000188:drug therapy; D001399:Azure Stains / Q000009:adverse effects*; D002091:Butyrylcholinesterase / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000009:adverse effects; D004791:Enzyme Inhibitors / Q000009:adverse effects; D006801:Humans; D020128:Inhibitory Concentration 50; D016014:Linear Models; D008751:Methylene Blue / Q000009:adverse effects*
chemical_list: D001399:Azure Stains; D002800:Cholinesterase Inhibitors; D004791:Enzyme Inhibitors; C025819:Azure B; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D008751:Methylene Blue
keywords: 5,5′-dithiobis(2-nitrobenzoic acid); AChE; Acetylcholinesterase; Alzheimer's disease; Azure B; BuChE; Butyrylcholinesterase; DTNB; Inhibition; MAO-A; MB; Methylene blue; acetylcholinesterase; butyrylcholinesterase; methylene blue; monoamine oxidase A