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Monoamine oxidase (generally referred to as MAO) is an enzyme that catalyzes (accelerates) the oxidative deamination of certain amines (see Image 1). MAO participates in the metabolism of monoamine neurotransmitters (serotonin, dopamine, norepinephrine, etc.) and many psychoactive drugs (tryptamines and phenethylamines) (Banik, 1990; Theobald & Maurer, 2006).
Two isoforms (similar variations) of MAO are present in humans: MAO-A and -B. These are distinguished based on their substrate specificities. Serotonin and norepinephrine are preferentially deaminated by MAO-A, and β-phenylethylamine is deaminated by MAO-B. Both MAO-A and -B deaminate dopamine (Banik, 1990).
MAO inhibitors (MAOIs) are substances that interfere with the enzyme's normal activity by binding to it. MAOIs are categorized based on their selectivity for MAO-A or -B and on the reversibility of the inhibition they cause (Holschneider & Shih, 2000).
Reversible MAOIs bind reversibly to MAO: they eventually detach, leaving the enzyme unchanged and active. Irreversible inhibitors (also known as inactivators or suicide inhibitors) form a covalent bond with MAO, leaving it permanently inactive (Banik, 1990). After irreversible inhibition, "recovery of enzymatic activity and restoration of amine metabolism generally requires up to two weeks, presumably because [MAO] must be replaced by synthesis" (Holschneider & Shih, 2000, sec. 6).
MAO inhibitors can be selective (show a preference for either MAO-A or -B at a given concentration) or non-selective (have approximately equal binding affinities for both isoforms). MAO inhibitors are virtually never 100% selective towards either isoform, gradually losing their selectivity at higher concentrations (citation needed).
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Banik GM. Mechanism-based inactivation of monoamine oxidase by (aminomethyl)trimethylsilane and (aminoethyl)trimethylsilane. Diss. Northwestern U, June 1990.
Theobald & Maurer. Identification of monoamine oxidase and cytochrome P450 isoenzymes involved in the deamination of phenethylamine-derived designer drugs (2C-series). Biochem Pharmacol 2006;69:287-97.
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Ramsay et al. Methylene blue and serotonin toxicity: inhibition of monoamine oxidase A (MAO A) confirms a theoretical prediction (abstract). Br J Pharmacol 2007 Nov;152(6):946-51.
Hemmateenejad et al. Partial least squares-based multivariate spectral calibration method for simultaneous determination of beta-carboline derivatives in Peganum harmala seed extracts (abstract). Anal Chim Acta 2006 Aug 11;575(2):290-9.
Holschneider, D. P., and Shih, J. C. (2000). "Monoamine Oxidase: Basic and Clinical Perspectives." Psychopharmacology - The Fourth Generation of Progress Retrieved on Feb 20, 2008 from http://www.acnp.org/g4/GN401000046/Default.htm
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