Monoamine oxidase B

{{Short description|Protein-coding gene in the species Homo sapiens}} {{cs1 config|name-list-style=vanc}} {{Use dmy dates|date=February 2015}} {{Infobox gene}}

'''Monoamine oxidase B''' ('''MAO-B''') is an enzyme that in humans is encoded by the ''MAOB'' gene.

The protein encoded by this gene belongs to the flavin monoamine oxidase family. It is an enzyme located in the outer mitochondrial membrane. It catalyzes the oxidative deamination of biogenic and xenobiotic amines and plays an important role in the catabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues. This protein preferentially degrades benzylamine and phenethylamine.<ref>{{cite web | title = Entrez Gene: MAOB monoamine oxidase B| url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=4129}}</ref> Similar to monoamine oxidase A (MAO-A), MAO-B is also involved in the catabolism of dopamine.<ref name="Tan_2022">{{cite journal |vauthors=Tan YY, Jenner P, Chen SD |date=2022 |title=Monoamine Oxidase-B Inhibitors for the Treatment of Parkinson's Disease: Past, Present, and Future |journal=Journal of Parkinson's Disease |volume=12 |issue=2 |pages=477–493 |doi=10.3233/JPD-212976 |pmc=8925102 |pmid=34957948 |quote=There are two MAO isoenzymes: MAO-A and MAO-B. MAO-A is mainly distributed in the gastrointestinal tract, platelets, and heart, and can promote the metabolism of tyramine-containing substances in food so avoiding hypertensive crises caused by the accumulation of tyramine ("cheese reaction"). MAO-A also exists in catecholaminergic neurons, such as dopaminergic neurons in SN, norepinephrine neurons in locus coeruleus, etc. [18]. MAO-B is mainly distributed in platelets and glial cells, and total MAO activity within the brain is composed of approximately 20% MAO-A and 80% MAO-B [19–22]. Both MAO-A and MAO-B regulate the amine neurotransmitters, including dopamine. MAO-A metabolizes dopamine in presynaptic neurons, while MAO-B metabolizes dopamine released to synaptic cleft and taken up by glial cells. The number of glial cells was shown to increase with age, and in neurodegenerative diseases, as expected, the activity of MAO-B also increased [23–25]. MAO-B inhibitors inhibit MAO-B activity in the brain, block dopamine catabolism, enhance dopamine signaling, and selectively enhance dopamine levels at synaptic cleft [21].}}</ref>{{Contradictory inline|reason=Referenced article seems to be based on outdated information; newer research mentioned later in this page indicates MAO-B is not responsible for degradation of dopamine.|date=February 2025}}

==Structure and function== MAO-B has a hydrophobic bipartite elongated cavity that (for the "open" conformation) occupies a combined volume close to 700 Å3. hMAO-A has a single cavity that exhibits a rounder shape and is larger in volume than the "substrate cavity" of hMAO-B.<ref name="pmid17573034">{{cite journal | vauthors = Edmondson DE, Binda C, Mattevi A | title = Structural insights into the mechanism of amine oxidation by monoamine oxidases A and B | journal = Arch. Biochem. Biophys. | volume = 464 | issue = 2 | pages = 269–76 | date = August 2007 | pmid = 17573034 | pmc = 1993809 | doi = 10.1016/j.abb.2007.05.006 }}</ref>

The first cavity of hMAO-B has been termed the ''entrance cavity'' (290 Å3), the second ''substrate cavity'' or ''active site cavity'' (~390 Å3) – between both an isoleucine199 side-chain serves as a ''gate''. Depending on the substrate or bound inhibitor, it can exist in either an open or a closed form, which has been shown to be important in defining the inhibitor specificity of hMAO-B. At the end of the substrate cavity is the FAD cofactor with sites for favorable amine binding about the flavin involving two nearly parallel tyrosyl (398 and 435) residues that form what has been termed an ''aromatic cage''.<ref name="pmid17573034"/>

Like MAO-A, MAO-B catalyzes O2-dependent oxidation of primary arylalkyl amines, the initial step in the breakdown of these molecules. The products are the corresponding aldehyde, hydrogen peroxide, and ammonia:

: Amine + {{chem|O|2}} + {{chem|H|2|O}} → Aldehyde + {{chem|H|2|O|2}} + {{chem|N|H|3}}

This reaction is believed to occur in three steps. First, the amine is oxidized to the corresponding imine, with reduction of the FAD cofactor to FADH2. Second, O2 accepts two electrons and two protons from FADH2, forming {{chem|H|2|O|2}} and regenerating FAD. Third, the imine is hydrolyzed by water, forming ammonia and the aldehyde.<ref name="pmid17573034" /><ref name=Binda>{{cite journal | vauthors = Binda C, Mattevi A, Edmondson DE | title = Structure-function relationships in flavoenzyme-dependent amine oxidations: A comparison of polyamine oxidase and monoamine oxidase | journal = Journal of Biological Chemistry | volume = 277 | issue = 27 | pages = 23973–23976 | date = July 5, 2002 | doi = 10.1074/jbc.R200005200 | pmid = 12015330 | doi-access = free }}</ref>

==Differences between MAO-A and MAO-B== MAO-A generally metabolizes tyramine, norepinephrine, serotonin, and dopamine (and other less clinically relevant chemicals). In contrast, MAO-B metabolizes dopamine{{Contradictory inline|reason=Next paragraph states that MAO-B was found to not be responsible for dopamine deamination.|date=February 2025}} and β-phenethylamine, as well as other less clinically relevant chemicals.<ref name="Bortolato_2018" /> The differences between the substrate selectivity of the two enzymes are utilized clinically when treating specific disorders; MAO-A inhibitors have been typically used in the treatment of depression, whereas MAO-B inhibitors are typically used in the treatment of Parkinson's disease.<ref name="pmid8313400">{{cite journal | vauthors = Nolen WA, Hoencamp E, Bouvy PF, Haffmans PM | title = Reversible monoamine oxidase-A inhibitors in resistant major depression | journal = Clin Neuropharmacol | volume = 16 | issue = Suppl 2 | pages = S69–76 | year = 1993 | pmid = 8313400 }}</ref><ref name="pmid22110357">{{cite journal | vauthors = Riederer P, Laux G | title = MAO-inhibitors in Parkinson's Disease | journal = Exp Neurobiol | volume = 20 | issue = 1 | pages = 1–17 | date = March 2011 | pmid = 22110357 | pmc = 3213739 | doi = 10.5607/en.2011.20.1.1 }}</ref> Concurrent use of MAO-A inhibitors with sympathomimetic drugs can induce a hypertensive crisis as a result of excessive norepinephrine.<ref name="Calvi_2021">{{cite journal | vauthors = Calvi A, Fischetti I, Verzicco I, Belvederi Murri M, Zanetidou S, Volpi R, Coghi P, Tedeschi S, Amore M, Cabassi A | display-authors = 6 | title = Antidepressant Drugs Effects on Blood Pressure | journal = Frontiers in Cardiovascular Medicine | volume = 8 | article-number = 704281 | date = 2021 | doi = 10.3389/fcvm.2021.704281 | doi-access = free | pmid = 34414219 | pmc = 8370473 | quote = The risk of developing the "cheese reaction" during treatment with MAOIs depends on the concurrent consumption of meals containing tyramine or sympathomimetic drugs (Table 3). Tyramine is normally metabolized by MAO-A located on the gut wall and by MAO-B in the liver; if MAO-A is inhibited, the bioavailability of tyramine is increased, which leads to an excess in NE, resulting in a hypertensive crisis (55, 217). Currently, they are not first-line antidepressant medications, and their use is limited to treatment-resistant or atypical depression. ... Selegiline is a selective MAO-B at low doses and a non-selective MAOI at higher doses; it also induces dopaminergic activity at low doses. This different action, depending on the dose, implies different use: low doses (up to 10 mg/day) for Parkinson's disease and higher doses as antidepressant treatment (Table 1) (55). ... Higher doses of oral and transdermal selegiline have been linked to a major frequency of orthostatic hypotension (227). No hypertensive crisis was reported with patch administration, but a small portion of patients with preexisting hypertension showed a worse BP control (224). }}</ref> Likewise, the consumption of tyramine-containing substances, such as cheese, whilst using MAO-A inhibitors also carries the risk of hypertensive crisis.<ref name="Tan_2022" /><ref name="Calvi_2021" /> Selective MAO-B inhibitors bypass this problem by preferentially inhibiting MAO-B, which allows tyramine to be metabolized freely by MAO-A in the gastrointestinal tract.<ref name="Tan_2022" /><ref name="Calvi_2021" />

In 2021, it was discovered that MAO-A completely or almost completely mediates striatal dopamine catabolism in the rodent brain and that MAO-B is not importantly involved.<ref name="NamSaJu2022">{{cite journal | vauthors = Nam MH, Sa M, Ju YH, Park MG, Lee CJ | title = Revisiting the Role of Astrocytic MAOB in Parkinson's Disease | journal = Int J Mol Sci | volume = 23 | issue = 8 | date = April 2022 | page = 4453 | pmid = 35457272 | pmc = 9028367 | doi = 10.3390/ijms23084453 | doi-access = free | url = }}</ref><ref name="ChoKimSim2021">{{cite journal | vauthors = Cho HU, Kim S, Sim J, Yang S, An H, Nam MH, Jang DP, Lee CJ | title = Redefining differential roles of MAO-A in dopamine degradation and MAO-B in tonic GABA synthesis | journal = Exp Mol Med | volume = 53 | issue = 7 | pages = 1148–1158 | date = July 2021 | pmid = 34244591 | pmc = 8333267 | doi = 10.1038/s12276-021-00646-3 | url = }}</ref> In contrast, MAO-B appears to mediate γ-aminobutyric acid (GABA) synthesis from putrescine in the striatum, a minor and alternative metabolic pathway of GABA synthesis, and this synthesized GABA in turn inhibits dopaminergic neurons in this brain area.<ref name="NamSaJu2022" /><ref name="ChoKimSim2021" /><ref name="WatanabeMaemuraKanbara2002">{{cite book | vauthors = Watanabe M, Maemura K, Kanbara K, Tamayama T, Hayasaki H | chapter = GABA and GABA Receptors in the Central Nervous System and Other Organs | title = A Survey of Cell Biology | journal = Int Rev Cytol | series = International Review of Cytology | volume = 213 | issue = | pages = 1–47 | date = 2002 | pmid = 11837891 | doi = 10.1016/s0074-7696(02)13011-7 | isbn = 978-0-12-364617-0 | chapter-url = }}</ref> MAO-B specifically mediates the transformations of putrescine into γ-aminobutyraldehyde (GABAL or GABA aldehyde) and ''N''-acetylputrescine into ''N''-acetyl-γ-aminobutyraldehyde (''N''-acetyl-GABAL or ''N''-acetyl-GABA aldehyde).<ref name="WatanabeMaemuraKanbara2002" /><ref name="Seiler2004">{{cite journal | vauthors = Seiler N | title = Catabolism of polyamines | journal = Amino Acids | volume = 26 | issue = 3 | pages = 217–233 | date = June 2004 | pmid = 15221502| doi = 10.1007/s00726-004-0070-z | url = }}</ref><ref name="NamSaJu2022" /><ref name="ChoKimSim2021" /> These findings may warrant a rethinking of the actions of MAO-B inhibitors in the treatment of Parkinson's disease.<ref name="NamSaJu2022" /><ref name="ChoKimSim2021" />

==Roles in disease and aging== Alzheimer's disease (AD) and Parkinson's disease (PD) are both associated with elevated levels of MAO-B in the brain.<ref name="pmid7816197">{{cite journal | vauthors = Saura J, Luque JM, Cesura AM, Da Prada M, Chan-Palay V, Huber G, Löffler J, Richards JG | display-authors = 6 | title = Increased monoamine oxidase B activity in plaque-associated astrocytes of Alzheimer brains revealed by quantitative enzyme radioautography | journal = Neuroscience | volume = 62 | issue = 1 | pages = 15–30 | date = September 1994 | pmid = 7816197 | doi = 10.1016/0306-4522(94)90311-5 | s2cid = 38740469 }}</ref><ref name="pmid19526285">{{cite journal | vauthors = Mallajosyula JK, Chinta SJ, Rajagopalan S, Nicholls DG, Andersen JK | title = Metabolic control analysis in a cellular model of elevated MAO-B: relevance to Parkinson's disease | journal = Neurotoxicity Research | volume = 16 | issue = 3 | pages = 186–193 | date = October 2009 | pmid = 19526285 | pmc = 2727365 | doi = 10.1007/s12640-009-9032-2 }}</ref> The normal activity of MAO-B creates reactive oxygen species, which directly damage cells.<ref name="pmid17447416">{{cite book | vauthors = Nagatsu T, Sawada M | chapter = Molecular mechanism of the relation of monoamine oxidase B and its inhibitors to Parkinson's disease: Possible implications of glial cells | title = Oxidative Stress and Neuroprotection | journal = Journal of Neural Transmission. Supplementum | volume = 71 | issue = 71 | pages = 53–65 | year = 2006 | pmid = 17447416 | doi = 10.1007/978-3-211-33328-0_7 | isbn = 978-3-211-33327-3 }}</ref> MAO-B levels have been found to increase with age, suggesting a role in natural age related cognitive decline and the increased likelihood of developing neurological diseases later in life.<ref name="pmid15247489">{{cite journal | vauthors = Kumar MJ, Andersen JK | title = Perspectives on MAO-B in aging and neurological disease: where do we go from here? | journal = Molecular Neurobiology | volume = 30 | issue = 1 | pages = 77–89 | date = August 2004 | pmid = 15247489 | doi = 10.1385/MN:30:1:077 | s2cid = 19776473 }}</ref> More active polymorphisms of the MAO-B gene have been linked to negative emotionality, and suspected as an underlying factor in depression.<ref name="pmid19657584">{{cite journal | vauthors = Dlugos AM, Palmer AA, de Wit H | title = Negative emotionality: monoamine oxidase B gene variants modulate personality traits in healthy humans | journal = Journal of Neural Transmission | volume = 116 | issue = 10 | pages = 1323–1334 | date = October 2009 | pmid = 19657584 | pmc = 3653168 | doi = 10.1007/s00702-009-0281-2 }}</ref> Activity of MAO-B has also been shown to play a role in stress-induced cardiac damage.<ref name="pmid20869994">{{cite journal | vauthors = Kaludercic N, Carpi A, Menabò R, Di Lisa F, Paolocci N | title = Monoamine oxidases (MAO) in the pathogenesis of heart failure and ischemia/reperfusion injury | journal = Biochimica et Biophysica Acta (BBA) - Molecular Cell Research | volume = 1813 | issue = 7 | pages = 1323–1332 | date = July 2011 | pmid = 20869994 | pmc = 3030628 | doi = 10.1016/j.bbamcr.2010.09.010 }}</ref><ref name="pmid23581564">{{cite journal | vauthors = Kaludercic N, Carpi A, Nagayama T, Sivakumaran V, Zhu G, Lai EW, Bedja D, De Mario A, Chen K, Gabrielson KL, Lindsey ML, Pacak K, Takimoto E, Shih JC, Kass DA, Di Lisa F, Paolocci N | display-authors = 6 | title = Monoamine oxidase B prompts mitochondrial and cardiac dysfunction in pressure overloaded hearts | journal = Antioxidants & Redox Signaling | volume = 20 | issue = 2 | pages = 267–280 | date = January 2014 | pmid = 23581564 | pmc = 3887464 | doi = 10.1089/ars.2012.4616 }}</ref> Over-expression and increased levels of MAO-B in the brain have also been linked to the accumulation of amyloid β-peptides (Aβ), through mechanisms of the amyloid precursor protein secretase, γ-secretase, responsible for the development of plaques, observed in Alzheimer's and Parkinson's patients. Evidence suggests that siRNA silencing of MAO-B, or inhibition of MAO-B through MAO-B inhibitors (Selegline, Rasagiline), slows the progression, improves and reverses the symptoms, associated with AD and PD, including the reduction of Aβ plaques in the brain.<ref>{{cite journal | vauthors = Schedin-Weiss S, Inoue M, Hromadkova L, Teranishi Y, Yamamoto NG, Wiehager B, Bogdanovic N, Winblad B, Sandebring-Matton A, Frykman S, Tjernberg LO | display-authors = 6 | title = Monoamine oxidase B is elevated in Alzheimer disease neurons, is associated with γ-secretase and regulates neuronal amyloid β-peptide levels | journal = Alzheimer's Research & Therapy | volume = 9 | issue = 1 | article-number = 57 | date = August 2017 | pmid = 28764767 | pmc = 5540560 | doi = 10.1186/s13195-017-0279-1 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Cai Z | title = Monoamine oxidase inhibitors: promising therapeutic agents for Alzheimer's disease (Review) | journal = Molecular Medicine Reports | volume = 9 | issue = 5 | pages = 1533–41 | date = May 2014 | pmid = 24626484 | doi = 10.3892/mmr.2014.2040 | doi-access = free }}</ref>

===Animal models=== Transgenic mice that are unable to produce MAO-B are shown to be resistant to a mouse model of Parkinson's disease.<ref name="pmid10591056">{{cite journal | vauthors = Shih JC, Chen K | title = MAO-A and -B gene knock-out mice exhibit distinctly different behavior | journal = Neurobiology (Bp) | volume = 7 | issue = 2 | pages = 235–46 | year = 1999 | pmid = 10591056 }}</ref><ref name="pmid9326944">{{cite journal | vauthors = Grimsby J, Toth M, Chen K, Kumazawa T, Klaidman L, Adams JD, Karoum F, Gal J, Shih JC | title = Increased stress response and beta-phenylethylamine in MAOB-deficient mice. | journal = Nature Genetics | volume = 17 | issue = 2 | pages = 206–10 | date = October 1997 | pmid = 9326944 | doi = 10.1038/ng1097-206 | s2cid = 31804364 }}</ref><ref>{{cite journal|author-link1=Jean Chen Shih | vauthors = Shih JC, Chen K, Ridd MJ | title = Monoamine oxidase: from genes to behavior. | journal = Annual Review of Neuroscience | volume = 22 | pages = 197–217 | year = 1999 | pmid = 10202537 | pmc = 2844879 | doi = 10.1146/annurev.neuro.22.1.197 }}</ref> They also demonstrate increased responsiveness to stress (as with MAO-A knockout mice)<ref name="Shih 21–30">{{cite journal | vauthors = Shih JC | title = Cloning, after cloning, knock-out mice, and physiological functions of MAO A and B. | journal = Neurotoxicology | volume = 25 | issue = 1–2 | pages = 21–30 | date = January 2004 | pmid = 14697877 | doi = 10.1016/s0161-813x(03)00112-8 | bibcode = 2004NeuTx..25...21S }}</ref> and increased β-PEA.<ref name="pmid9326944" /><ref name="Shih 21–30"/> In addition, they exhibit behavioral disinhibition and reduced anxiety-like behaviors.<ref>{{cite journal | vauthors = Bortolato M, Godar SC, Davarian S, Chen K, Shih JC | title = Behavioral disinhibition and reduced anxiety-like behaviors in monoamine oxidase B-deficient mice. | journal = Neuropsychopharmacology | volume = 34 | issue = 13 | pages = 2746–57 | date = December 2009 | pmid = 19710633 | pmc = 2783894 | doi = 10.1038/npp.2009.118 }}</ref>

Treatment with selegiline, an MAO-B inhibitor, in rats has been shown to prevent many age-related biological changes, such as optic nerve degeneration, and extend average lifespan by up to 39%.<ref name="pmid23082958">{{cite journal | vauthors = Nebbioso M, Pascarella A, Cavallotti C, Pescosolido N | title = Monoamine oxidase enzymes and oxidative stress in the rat optic nerve: age-related changes | journal = International Journal of Experimental Pathology | volume = 93 | issue = 6 | pages = 401–5 | date = December 2012 | pmid = 23082958 | pmc = 3521895 | doi = 10.1111/j.1365-2613.2012.00832.x }}</ref><ref name="pmid8423709">{{cite journal | vauthors = Kitani K, Kanai S, Sato Y, Ohta M, Ivy GO, Carrillo MC | title = Chronic treatment of (-)deprenyl prolongs the life span of male Fischer 344 rats. Further evidence | journal = Life Sci. | volume = 52 | issue = 3 | pages = 281–8 | year = 1993 | pmid = 8423709 | doi = 10.1016/0024-3205(93)90219-S }}</ref> However, subsequent research suggests that the anti-aging effects of selegiline in animals are due to its catecholaminergic activity enhancer actions rather than MAO-B inhibition.<ref name="Miklya2016">{{cite journal | vauthors = Miklya I | title = The significance of selegiline/(-)-deprenyl after 50 years in research and therapy (1965-2015) | journal = Mol Psychiatry | volume = 21 | issue = 11 | pages = 1499–1503 | date = November 2016 | pmid = 27480491 | doi = 10.1038/mp.2016.127 | url =https://repo.lib.semmelweis.hu//bitstream/123456789/6530/4/Miklya_mp2016127.pdf }}</ref>

===Effects of deficiency in humans=== While people lacking the gene for MAO-A display intellectual disabilities and behavioral abnormalities, people lacking the gene for MAO-B display no abnormalities except elevated phenethylamine levels in urine.<ref>{{cite book | vauthors = Bortolato M, Shih JC | title = Monoamine Oxidase and their Inhibitors | chapter = Behavioral outcomes of monoamine oxidase deficiency: preclinical and clinical evidence | series = International Review of Neurobiology | volume = 100 | pages = 13–42 | date = 2011 | pmid = 21971001 | pmc = 3371272 | doi = 10.1016/B978-0-12-386467-3.00002-9 | isbn = 978-0-12-386467-3 | quote = To the best of our knowledge, there have been no reports of clinical conditions characterized by selective MAO-B deficiency. However, in few cases of atypical ND with MAO-B deletion, the latter deficit was reported to result in increased urinary excretion of PEA, but no overt behavioral abnormalities or cognitive deficits (Berger et al., 1992; Lenders et al., 1996). }}</ref><ref name="Bortolato_2018">{{cite journal | vauthors = Bortolato M, Floris G, Shih JC | title = From aggression to autism: new perspectives on the behavioral sequelae of monoamine oxidase deficiency | journal = Journal of Neural Transmission | volume = 125 | issue = 11 | pages = 1589–1599 | date = November 2018 | pmid = 29748850 | pmc = 6215718 | doi = 10.1007/s00702-018-1888-y | quote = In striking contrast with the evidence on MAOA deficiency, the clinical consequences of low MAO B activity remain partially elusive. Indeed, the only cases with a documented loss-of-function mutation were described in atypical Norrie disease patients, harboring deletions of both the ND gene as well as the (adjacent) MAOB gene (Lenders et al., 1996). These patients did not exhibit any overt psychopathological alterations, pointing to a lack of overt clinical sequelae of MAOB deficiency (Lenders et al., 1996). ... The behavioral sequelae of MAO B deficiency are unlikely to be reflective of early neurodevelopmental problems (given the lower expression of this enzyme in perinatal stages), but may instead reflect tonic enhancements of PEA and/or other MAO B substrates. PEA is a trace amine that has been involved in several neuropsychiatric disorders (Beckmann et al., 1983; Szymanski et al., 1987; O'Reilly et al., 1991; Berry, 2007). The effects of PEA are not fully clear, but its chemical similarity with d-amphetamine (in which a methyl group is substituted at the α-carbon) underlines the possibility that this molecule may serve as a facilitator of catecholamine and serotonin release. On the other hand, the identification of TAAR1 as the endogenous receptor for PEA, as well as other monoamines metabolized by MAO B (such as tyramine and 3-iodothyronamine), calls into question whether the effects of PEA may result from a combination of different mechanisms. }}</ref>

The prophylactic use of MAO-B inhibitors to slow human aging in otherwise healthy individuals has been proposed, but remains a highly controversial topic.<ref name="pmid20150659">{{cite journal | vauthors = Miklya I | title = [Slowing the age-induced decline of brain function with prophylactic use of (−)-deprenyl (Selegiline, Jumex). Current international view and conclusions 25 years after the Knoll's proposal] | language = hu | journal = Neuropsychopharmacol Hung | volume = 11 | issue = 4 | pages = 217–25 | date = December 2009 | pmid = 20150659 }}</ref><ref name="pmid15246996">{{cite journal | vauthors = Ukraintseva SV, Arbeev KG, Michalsky AI, Yashin AI | title = Antiaging treatments have been legally prescribed for approximately thirty years | journal = Ann. N. Y. Acad. Sci. | volume = 1019 | pages = 64–9 | date = June 2004 | issue = 1 | pmid = 15246996 | doi = 10.1196/annals.1297.014 | bibcode = 2004NYASA1019...64U | s2cid = 25181147 }}</ref>

Species-dependent divergences may hamper the extrapolation of inhibitor potencies.<ref name="pmid17034132">{{cite journal | vauthors = Novaroli L, Daina A, Favre E, Bravo J, Carotti A, Leonetti F, Catto M, Carrupt PA, Reist M | title = Impact of species-dependent differences on screening, design, and development of MAO B inhibitors | journal = J. Med. Chem. | volume = 49 | issue = 21 | pages = 6264–72 | date = October 2006 | pmid = 17034132 | doi = 10.1021/jm060441e }}</ref>

===Reversible=== ====Natural==== * Geiparvarin<ref name="pmid12443774">{{cite journal | vauthors = Carotti A, Carrieri A, Chimichi S, Boccalini M, Cosimelli B, Gnerre C, Carotti A, Carrupt PA, Testa B | title = Natural and synthetic geiparvarins are strong and selective MAO-B inhibitors. Synthesis and SAR studies | journal = Bioorg. Med. Chem. Lett. | volume = 12 | issue = 24 | pages = 3551–5 | date = December 2002 | pmid = 12443774 | doi = 10.1016/S0960-894X(02)00798-9 }}</ref> * Desmethoxyyangonin,<ref name="pmid9832350">{{cite journal | vauthors = Uebelhack R, Franke L, Schewe HJ | title = Inhibition of platelet MAO-B by kava pyrone-enriched extract from Piper methysticum Forster (kava-kava) | journal = Pharmacopsychiatry | volume = 31 | issue = 5 | pages = 187–92 | date = September 1998 | pmid = 9832350 | doi = 10.1055/s-2007-979325 | s2cid = 25270815 }}</ref> a constituent of kava extract; modest affinity * Catechin and epicatechin{{Citation needed|reason=This is a bold claim with many important consequences|date=February 2020}}. * Garlic<ref>{{cite journal | vauthors = Dhingra D, Kumar V | title = Evidences for the involvement of monoaminergic and GABAergic systems in antidepressant-like activity of garlic extract in mice | journal = Indian Journal of Pharmacology | volume = 40 | issue = 4 | pages = 175–179 | date = August 2008 | pmid = 20040952 | pmc = 2792615 | doi = 10.4103/0253-7613.43165 | doi-access = free }}</ref> * Rosiridin<ref>{{cite journal | vauthors = van Diermen D, Marston A, Bravo J, Reist M, Carrupt PA, Hostettmann K | title = Monoamine oxidase inhibition by Rhodiola rosea L. roots | journal = Journal of Ethnopharmacology | volume = 122 | issue = 2 | pages = 397–401 | date = March 2009 | pmid = 19168123 | doi = 10.1016/j.jep.2009.01.007 | bibcode = 2009JEthn.122..397V }}</ref> (''in vitro'')

==== Synthetic ==== * Safinamide and analogs<ref name="pmid17824599">{{cite journal | vauthors = Leonetti F, Capaldi C, Pisani L, Nicolotti O, Muncipinto G, Stefanachi A, Cellamare S, Caccia C, Carotti A | title = Solid-phase synthesis and insights into structure-activity relationships of safinamide analogues as potent and selective inhibitors of type B monoamine oxidase | journal = Journal of Medicinal Chemistry | volume = 50 | issue = 20 | pages = 4909–16 | date = October 2007 | pmid = 17824599 | doi = 10.1021/jm070725e }}</ref> * 5''H''-Indeno[1,2-c]pyridazin-5-ones<ref name="pmid17034132"/><ref name="pmid16759116">compound #2d, {{cite journal | vauthors = Frédérick R, Dumont W, Ooms F, Aschenbach L, Van der Schyf CJ, Castagnoli N, Wouters J, Krief A | title = Synthesis, structural reassignment, and biological activity of type B MAO inhibitors based on the 5H-indeno[1,2-c]pyridazin-5-one core | journal = J. Med. Chem. | volume = 49 | issue = 12 | pages = 3743–7 |date=June 2006 | pmid = 16759116 | doi = 10.1021/jm051091j }}</ref><ref name="pmid17910428">{{cite journal | vauthors = Carotti A, Catto M, Leonetti F, Campagna F, Soto-Otero R, Méndez-Alvarez E, Thull U, Testa B, Altomare C | title = Synthesis and monoamine oxidase inhibitory activity of new pyridazine-, pyrimidine- and 1,2,4-triazine-containing tricyclic derivatives | journal = Journal of Medicinal Chemistry | volume = 50 | issue = 22 | pages = 5364–71 | date = November 2007 | pmid = 17910428 | doi = 10.1021/jm070728r }}</ref> (see 3d model) * Substituted chalcones<ref name="pmid19378991">{{cite journal | vauthors = Chimenti F, Fioravanti R, Bolasco A, Chimenti P, Secci D, Rossi F, Yáñez M, Orallo F, Ortuso F, Alcaro S | title = Chalcones: a valid scaffold for monoamine oxidases inhibitors | journal = J. Med. Chem. | volume = 52 | issue = 9 | pages = 2818–24 | date = May 2009 | pmid = 19378991 | doi = 10.1021/jm801590u }}</ref> * 2-(''N''-Methyl-''N''-benzylaminomethyl)-1''H''-pyrrole<ref name="pmid12620068">compound #21, {{cite journal | vauthors = Silvestri R, La Regina G, De Martino G, Artico M, Befani O, Palumbo M, Agostinelli E, Turini P | title = Simple, potent, and selective pyrrole inhibitors of monoamine oxidase types A and B | journal = J. Med. Chem. | volume = 46 | issue = 6 | pages = 917–20 | date = March 2003 | pmid = 12620068 | doi = 10.1021/jm0256124 }}</ref> * 1-(4-Arylthiazol-2-yl)-2-(3-methylcyclohexylidene)hydrazine<ref name="pmid20715818">compound # (''R'')-8b, {{cite journal | vauthors = Chimenti F, Secci D, Bolasco A, Chimenti P, Granese A, Carradori S, Yáñez M, Orallo F, Sanna ML, Gallinella B, Cirilli R | title = Synthesis, stereochemical separation, and biological evaluation of selective inhibitors of human MAO-B: 1-(4-arylthiazol-2-yl)-2-(3-methylcyclohexylidene)hydrazines | journal = J. Med. Chem. | volume = 53 | issue = 17 | pages = 6516–20 | date = September 2010 | pmid = 20715818 | doi = 10.1021/jm100120s | hdl = 11573/360702 | hdl-access = free }}</ref> * 2-Thiazolylhydrazone<ref name="pmid17253676">compound #18, {{cite journal | vauthors = Chimenti F, Maccioni E, Secci D, Bolasco A, Chimenti P, Granese A, Befani O, Turini P, Alcaro S, Ortuso F, Cardia MC, Distinto S | title = Selective inhibitory activity against MAO and molecular modeling studies of 2-thiazolylhydrazone derivatives | journal = J. Med. Chem. | volume = 50 | issue = 4 | pages = 707–12 | date = February 2007 | pmid = 17253676 | doi = 10.1021/jm060869d | hdl = 11573/231039 }}</ref> * 3,5-Diaryl pyrazole<ref name="pmid17266193">compound #3g, {{cite journal | vauthors = Chimenti F, Fioravanti R, Bolasco A, Manna F, Chimenti P, Secci D, Befani O, Turini P, Ortuso F, Alcaro S | title = Monoamine oxidase isoform-dependent tautomeric influence in the recognition of 3,5-diaryl pyrazole inhibitors | journal = J. Med. Chem. | volume = 50 | issue = 3 | pages = 425–8 | date = February 2007 | pmid = 17266193 | doi = 10.1021/jm060868l }}</ref> * Pyrazoline derivatives<ref name="pmid16279769">compound #(''S'')-1, {{cite journal | vauthors = Chimenti F, Maccioni E, Secci D, Bolasco A, Chimenti P, Granese A, Befani O, Turini P, Alcaro S, Ortuso F, Cirilli R, La Torre F, Cardia MC, Distinto S | title = Synthesis, molecular modeling studies, and selective inhibitory activity against monoamine oxidase of 1-thiocarbamoyl-3,5-diaryl-4,5-dihydro-(1H)- pyrazole derivatives | journal = J. Med. Chem. | volume = 48 | issue = 23 | pages = 7113–22 | date = November 2005 | pmid = 16279769 | doi = 10.1021/jm040903t }}</ref><ref name="pmid21377879">{{cite journal | vauthors = Mishra N, Sasmal D | title = Development of selective and reversible pyrazoline based MAO-B inhibitors: virtual screening, synthesis and biological evaluation | journal = Bioorg. Med. Chem. Lett. | volume = 21 | issue = 7 | pages = 1969–73 | date = April 2011 | pmid = 21377879 | doi = 10.1016/j.bmcl.2011.02.030 }}</ref> * Several coumarin derivatives<ref name = "pmid16884303">compound #41, {{cite journal | vauthors = Catto M, Nicolotti O, Leonetti F, Carotti A, Favia AD, Soto-Otero R, Méndez-Alvarez E, Carotti A | title = Structural insights into monoamine oxidase inhibitory potency and selectivity of 7-substituted coumarins from ligand- and target-based approaches | journal = Journal of Medicinal Chemistry | volume = 49 | issue = 16 | pages = 4912–25 | year = 2006 | pmid = 16884303 | doi = 10.1021/jm060183l }}</ref> and #C19*<ref name="pmid17034132"/> (see 3d model) * Phenylcoumarins, extremely subtype selective<ref name="pmid21684743">compound #2, {{cite journal | vauthors = Matos MJ, Vazquez-Rodriguez S, Uriarte E, Santana L, Viña D | title = MAO inhibitory activity modulation: 3-Phenylcoumarins versus 3-benzoylcoumarins | journal = Bioorg. Med. Chem. Lett. | volume = 21 | issue = 14 | pages = 4224–7 |date=July 2011 | pmid = 21684743 | doi = 10.1016/j.bmcl.2011.05.074 }}</ref> and further analogs<ref name="pmid20659799">{{cite journal | vauthors = Matos MJ, Viña D, Janeiro P, Borges F, Santana L, Uriarte E | title = New halogenated 3-phenylcoumarins as potent and selective MAO-B inhibitors | journal = Bioorg. Med. Chem. Lett. | volume = 20 | issue = 17 | pages = 5157–60 | date = September 2010 | pmid = 20659799 | doi = 10.1016/j.bmcl.2010.07.013 }}</ref><ref name="pmid19628387">{{cite journal | vauthors = Matos MJ, Viña D, Picciau C, Orallo F, Santana L, Uriarte E | title = Synthesis and evaluation of 6-methyl-3-phenylcoumarins as potent and selective MAO-B inhibitors | journal = Bioorg. Med. Chem. Lett. | volume = 19 | issue = 17 | pages = 5053–5 | date = September 2009 | pmid = 19628387 | doi = 10.1016/j.bmcl.2009.07.039 }}</ref><ref name="pmid19423346">{{cite journal | vauthors = Matos MJ, Viña D, Quezada E, Picciau C, Delogu G, Orallo F, Santana L, Uriarte E | title = A new series of 3-phenylcoumarins as potent and selective MAO-B inhibitors | journal = Bioorg. Med. Chem. Lett. | volume = 19 | issue = 12 | pages = 3268–70 | date = June 2009 | pmid = 19423346 | doi = 10.1016/j.bmcl.2009.04.085 }}</ref> (see 3d model) * Chromone-3-phenylcarboxamides<ref name="pmid21194943">compound #9, #12, {{cite journal | vauthors = Gaspar A, Reis J, Fonseca A, Milhazes N, Viña D, Uriarte E, Borges F | title = Chromone 3-phenylcarboxamides as potent and selective MAO-B inhibitors | journal = Bioorg. Med. Chem. Lett. | volume = 21 | issue = 2 | pages = 707–9 | date = January 2011 | pmid = 21194943 | doi = 10.1016/j.bmcl.2010.11.128 }}</ref> * Isatins<ref name="pmid21134756">compound #9i, {{cite journal | vauthors = Manley-King CI, Bergh JJ, Petzer JP | title = Inhibition of monoamine oxidase by selected C5- and C6-substituted isatin analogues | journal = Bioorg. Med. Chem. | volume = 19 | issue = 1 | pages = 261–74 | date = January 2011 | pmid = 21134756 | doi = 10.1016/j.bmc.2010.11.028 }}</ref> * Phthalimides<ref name="pmid21778064">compound #5c, {{cite journal | vauthors = Manley-King CI, Bergh JJ, Petzer JP | title = Inhibition of monoamine oxidase by C5-substituted phthalimide analogues | journal = Bioorg. Med. Chem. | volume = 19 | issue = 16 | pages = 4829–40 | date = August 2011 | pmid = 21778064 | doi = 10.1016/j.bmc.2011.06.070 }}</ref> * 8-Benzyloxycaffeines<ref name="pmid21621312">{{cite journal | vauthors = Strydom B, Bergh JJ, Petzer JP | title = 8-Aryl- and alkyloxycaffeine analogues as inhibitors of monoamine oxidase | journal = Eur J Med Chem | volume = 46 | issue = 8 | pages = 3474–85 | date = August 2011 | pmid = 21621312 | doi = 10.1016/j.ejmech.2011.05.014 }}</ref><ref name="pmid20093036">{{cite journal | vauthors = Strydom B, Malan SF, Castagnoli N, Bergh JJ, Petzer JP | title = Inhibition of monoamine oxidase by 8-benzyloxycaffeine analogues | journal = Bioorg. Med. Chem. | volume = 18 | issue = 3 | pages = 1018–28 | date = February 2010 | pmid = 20093036 | doi = 10.1016/j.bmc.2009.12.064 }}</ref> and CSC analogs<ref name="pmid16442801">{{cite journal | vauthors = Vlok N, Malan SF, Castagnoli N, Bergh JJ, Petzer JP | title = Inhibition of monoamine oxidase B by analogues of the adenosine A2A receptor antagonist (E)-8-(3-chlorostyryl)caffeine (CSC) | journal = Bioorg. Med. Chem. | volume = 14 | issue = 10 | pages = 3512–21 | date = May 2006 | pmid = 16442801 | doi = 10.1016/j.bmc.2006.01.011 }}</ref> * (''E,E'')-8-(4-phenylbutadien-1-yl)caffeines,<ref name="pmid18723354">{{cite journal | vauthors = Pretorius J, Malan SF, Castagnoli N, Bergh JJ, Petzer JP | title = Dual inhibition of monoamine oxidase B and antagonism of the adenosine A(2A) receptor by (E,E)-8-(4-phenylbutadien-1-yl)caffeine analogues | journal = Bioorganic & Medicinal Chemistry | volume = 16 | issue = 18 | pages = 8676–84 | date = September 2008 | pmid = 18723354 | doi = 10.1016/j.bmc.2008.07.088 }}</ref> with A2A antagonistic component * Indazole- and Indole-5-carboxamides<ref>{{cite journal | vauthors = Tzvetkov NT, Hinz S, Küppers P, Gastreich M, Müller CE | title = Indazole- and indole-5-carboxamides: selective and reversible monoamine oxidase B inhibitors with subnanomolar potency | journal = Journal of Medicinal Chemistry | volume = 57 | issue = 15 | pages = 6679–6703 | date = August 2014 | pmid = 24955776 | doi = 10.1021/jm500729a }}</ref>

=== Irreversible (covalent) === * Selegiline (Eldepryl, Zelapar, Emsam) * Rasagiline (Azilect)

== See also == * Monoamine oxidase A {{Clear}}

== References == {{Reflist|30em}}

{{Mitochondrial enzymes}} {{Neurotransmitter metabolism enzymes}} {{CH-NH2 oxidoreductases}} {{Enzymes}} {{Monoamine metabolism modulators}} {{Portal bar|Biology|border=no}}

Category:EC 1.4.3 Category:Human proteins