Monoamine oxidase

Introduction to monoamine oxidase

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

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).

Column 1 Column 2 Column 3
MAOIs in medical use Excluding withdrawn, abandoned, and experimental MAOIs
Isocarboxazid (Marplan) Antidepressant. Irreversible, non-selective (Riederer et al., 2004).
Phenelzine (Nardil) Antidepressant. Irreversible, non-selective (Riederer et al., 2004).
Tranylcypromine (Parnate) Antidepressant. Irreversible, non-selective (Riederer et al., 2004).
Moclobemide (Aurorix) Antidepressant. Reversible, MAO-A selective (RIMA) (Riederer et al., 2004). selectivity loss
Toloxatone (Humoryl) Antidepressant. Reversible, MAO-A selective (RIMA) (Riederer et al., 2004).
Selegiline (Eldepryl, Emsam, Zelapar) Anti-parkinson. Irreversible, MAO-B selective Loses selectivity above 10 mg/day (Holschneider & Shih, sec. 6). bioavailability
Rasagiline (Azilect) Anti-parkinson. Irreversible, MAO-B selective (Riederer et al., 2004).
Linezolid (Zyvox, Zyvoxid) Antibiotic. Reversible, non-selective (Taylor et al., 2006).
Furazolidone (Furoxone) Antibiotic. reversibility, selectivity
Procarbazine (Matulane) Antineoplastic. reversibility, selectivity
Methylene Blue Redox dye. Reversible, MAO-A selective (RIMA). Related redox dyes (toluidine blue O, thionine, brilliant cresyl blue, toluylene blue) are also RIMAs (Ramsay et al., 2007; Oxenkrug et al., 2007).

Column 1 Column 2 Column 3
Recreationally used MAOIs Including "research chemicals"
Coffee Contains significant amounts of norharman (β-carboline) and harman (1-methyl-β-carboline), which are reversible MAO inhibitors (Herraiz & Chaparro, 2006). The hypothesis that coffee consumption lowers MAO activity in humans was not yet demonstrated.
Tobacco Smokers have approximately 20-30% lower MAO-A activity and approximately 30-40% lower MAO-B activity than non-smokers (Fowler et al., 1996; Berlin & Anthenelli 2001, Fowler et al 2003). Tobacco smoke contains norharman (β-carboline) and harman (1-methyl-β-carboline), which are partially responsible for MAO inhibition in smokers (Herrais & Chaparro, 2005). Because overnight abstinence (11.3 hours) from smoking does not cause any significant normalization of brain MAO-B activity in smokers (Fowler et al., 2000) and tobacco smoke was found to irreversibly inhibit MAO in vitro (Yu & Boulton, 1987), tobacco should be considered an irreversible MAO inhibitor, although it is a mild one.
Harmine & related Reversible, MAO-A selective (RIMA) (Kim et al., 1997, Wouters, 1988). Present in Peganum harmala (Syrian Rue) (Hemmateenejad et al., 2006) and Banisteriopsis caapi (Yagé) (Callaway et al., 2005). other beta-carbolines
α-Methyltryptamine (AMT) Reversible, MAO-A selective (RIMA) (Arai et al., 1986; Renyi, 1986). 5-MeO-AMT
α-Ethyltryptamine (etryptamine, AET) Reversible, MAO-A selective (RIMA) (Renyi, 1986).
4-methylthioamphetamine (4-MTA) Reversible, MAO-A selective (RIMA) (Hurtado-Guzman et al., 2003).
2C-T-series 2,5-dimethoxy-4-thiophenethylamine derivatives

Column 1 Column 2 Column 3
Other MAOIs Foods, herbals, and other miscellaneous MAOIs
Nutmeg Myristicin, the major component of the essential oil of nutmeg, is considered a weak MAOI. MAO inhibition may be significant when large amounts are ingested (citation needed).

Food interactions with MAO inhibitors

This section needs to be written.

Drug interactions with MAO inhibitors

This section needs to be written.


Herrais & Chaparro. Human monoamine oxidase is inhibited by tobacco smoke: beta-carboline alkaloids act as potent and reversible inhibitors (abstract). Biochem Biophys Res Commun 2005 Jan 14;326(2):378-86.

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.

Shih et al. Role of MAO A and B in neurotransmitter metabolism and behavior (abstract). Pol J Pharmacol 1999 Jan-Feb;51(1):25-9.

Fowler et al. Brain monoamine oxidase A inhibition in cigarette smokers. PNAS 1996 Nov;93(24):14065-9.

Berlin & Anthenelli. Monoamine oxidases and tobacco smoking (abstract). Int J Neuropsychopharmacol 2001 Mar;4(1):33-42.

Fowler et al. Low monoamine oxidase B in peripheral organs in smokers. PNAS 2003 Sep 30;100(20):11600-5.

Fowler et al. Maintenance of brain monoamine oxidase B inhibition in smokers after overnight cigarette abstinence. Am J Psychiatry 2000 Nov;157(11):1864-6.

Yu & Boulton. Irreversible inhibition of monoamine oxidase by some components of cigarette smoke (abstract). Life Sci 1987 Aug 10;41(6):675-82.

Oxenkrug et al. Effect of methylene blue and related redox dyes on monoamine oxidase activity; rat pineal content of N-acetylserotonin, melatonin, and related indoles; and righting reflex in melatonin-primed frogs (abstract). Ann NY Acad Sci 2007 Dec;1122:245-52.

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

Callaway et al. Phytochemical analysis of Banisteriopsis caapi and Psychotria viridis. J Psychoactive Drugs 2005 Jun;37(2):145-50.

Kim et al. Inhibition of monoamine oxidase A by beta-carboline derivatives (abstract). Arch Biochem Biophys 1997 Jan 1;337(1):137-42.

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