Methylene blue and serotonin toxicity: inhibition of monoamine oxidase A (MAO A) confirms a theoretical prediction
- 1 November 2007
- journal article
- Published by Wiley in British Journal of Pharmacology
- Vol. 152 (6), 946-951
- https://doi.org/10.1038/sj.bjp.0707430
Abstract
Monoamine oxidase inhibitors (MAOI) are known to cause serotonin toxicity (ST) when administered with selective serotonin reuptake inhibitors (SSRI). Methylene blue (methylthionium chloride, MB), a redox dye in clinical use, has been reported to precipitate ST in patients using SSRI. MB was assessed for MAO inhibition and so for its potential to precipitate ST. Inhibition of purified human MAO was quantified using kinetic assays and visible spectral changes to study the interactions of MB with MAO A. MB was a potent (tight binding) inhibitor for MAO A. It also inhibited MAO B but at much higher concentration. Interactions of MB with the active site of MAO A were confirmed by its action both as an oxidising substrate and as a one-electron reductant. MB is a potent reversible inhibitor of MAO A with implications for gut uptake of amines when administered orally. At concentrations reported in the literature after intravenous administration, MAO B would be partially inhibited but MAO A would be completely inhibited. This inhibition of MAO A would be expected to lead to perturbations of 5-hydroxytryptamine metabolism and hence account for ST occurring when administered to patients on SSRI treatment.Keywords
This publication has 69 references indexed in Scilit:
- MEME SUITE: tools for motif discovery and searchingNucleic Acids Research, 2009
- PeakSeq enables systematic scoring of ChIP-seq experiments relative to controlsNature Biotechnology, 2009
- An integrated software system for analyzing ChIP-chip and ChIP-seq dataNature Biotechnology, 2008
- Genome-wide analysis of transcription factor binding sites based on ChIP-Seq dataNature Methods, 2008
- Genome-wide identification ofin vivoprotein-DNA binding sites from ChIP-Seq dataNucleic Acids Research, 2008
- FindPeaks 3.1: a tool for identifying areas of enrichment from massively parallel short-read sequencing technologyBioinformatics, 2008
- Integration of External Signaling Pathways with the Core Transcriptional Network in Embryonic Stem CellsCell, 2008
- Mapping and quantifying mammalian transcriptomes by RNA-SeqNature Methods, 2008
- A framework for collaborative analysis of ENCODE data: Making large-scale analyses biologist-friendlyGenome Research, 2007
- A gene atlas of the mouse and human protein-encoding transcriptomesProceedings of the National Academy of Sciences of the United States of America, 2004