Monoamine oxidase B

Monoamine oxidase B, also known as MAOB, is an enzyme that in humans is encoded by the MAOB gene.

Available structures
PDBOrtholog search: PDBe RCSB
AliasesMAOB, Monoamine oxidase B
External IDsOMIM: 309860 MGI: 96916 HomoloGene: 20251 GeneCards: MAOB
Gene location (Human)
Chr.X chromosome (human)[1]
BandXp11.3Start43,766,610 bp[1]
End43,882,450 bp[1]
RNA expression pattern
More reference expression data









RefSeq (mRNA)



RefSeq (protein)



Location (UCSC)Chr X: 43.77 – 43.88 MbChr X: 16.71 – 16.82 Mb
PubMed search[3][4]
View/Edit HumanView/Edit Mouse

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 phenylethylamine.[5] Like MAOA, it also degrades dopamine.


Monoamine oxidase 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.[6]

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 coenzyme 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.[6]

Differences between MAOA and MAOB

MAO-A is involved in the metabolism of tyramine; inhibition, in particular irreversible inhibition of MAO-A can result in a dangerous pressor effect when foods high in tyramine are consumed such as cheeses (informally known as the "cheese effect"). MAO-A is involved in the metabolism of serotonin, noradrenaline and dopamine whereas MAO-B metabolises the dopamine neurotransmitter.[7] MAO-B is an enzyme on the outer mitochondrial membrane and catalyzes the oxidation of arylalkylamine neurotransmitters[8]

Monoamine oxidase A (MAOA) generally metabolizes tyramine, norepinephrine (NE), serotonin (5-HT), and dopamine (DA) (and other less clinically relevant chemicals). In contrast, Monoamine oxidase B (MAOB) mainly metabolizes dopamine (DA) (and other less clinically relevant chemicals). The differences between the substrate selectivity of the two enzymes are utilized clinically when treating specific disorders: Monoamine oxidase A inhibitors have been typically used in the treatment of depression, and monoamine oxidase B inhibitors are typically used in the treatment of Parkinson's disease.[9][10] Nonspecific (i.e. MAOA/B combined) inhibitors can pose problems when taken concomitantly with tyramine-containing foods such as cheese, because the drug's inhibition of MAOA causes a dangerous elevation of serum tyramine levels, which can lead to hypertensive symptoms. Selective MAOB inhibitors bypass this problem by preferentially inhibiting MAOB, which mostly metabolizes DA. If MAOB is inhibited, then more DA is available for proper neuronal function, especially in Parkinson's Disease.

Roles in disease and aging

Alzheimer's disease and Parkinson's disease are both associated with elevated levels of MAO-B in the brain.[11][12] The normal activity of MAO-B creates reactive oxygen species, which directly damage cells.[13] 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.[14] More active polymorphisms of the MAOB gene have been linked to negative emotionality, and suspected as an underlying factor in depression.[15] Activity of MAO-B has also been shown to play a role in stress-induced cardiac damage.[16][17]

Animal models

Transgenic mice that are unable to produce MAO-B are shown to be resistant to a mouse model of Parkinson's disease.[18][19][20] They also demonstrate increased responsiveness to stress (as with MAO-A knockout mice)[21] and increased β-PEA.[19][21] In addition, they exhibit behavioral disinhibition and reduced anxiety-like behaviors.[22]

Inhibition of MAO-B 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%.[23][24]

Effects of deficiency in humans

While people lacking the gene for MAO-A display mental retardation and behavioral abnormalities, people lacking the gene for MAO-B display no abnormalities except elevated phenethylamine levels in urine, raising the question of whether MAO-B is actually a necessary enzyme. Newer research indicates the importance of phenethylamine and other trace amines, which are now known to regulate catecholamine and serotonin neurotransmission through the same receptor as amphetamine, TAAR1.[25][26]

The prophylactic use of MAO-B inhibitors to slow natural human aging in otherwise healthy individuals has been proposed, but remains a highly controversial topic.[27][28]

Selective inhibitors

Structural formulae of high-affinity reversible MAO inhibitors selective for type B

Species-dependent divergences may hamper the extrapolation of inhibitor potencies.[29]




  • Safinamide and analogs[33]
  • 5H-Indeno[1,2-c]pyridazin-5-ones[29][34][35] (see 3d model)
  • Substituted chalcones[36]
  • 2-(N-Methyl-N-benzylaminomethyl)-1H-pyrrole[37]
  • 1-(4-Arylthiazol-2-yl)-2-(3-methylcyclohexylidene)hydrazine[38]
  • 2-Thiazolylhydrazone[39]
  • 3,5-Diaryl pyrazole[40]
  • Pyrazoline derivatives[41][42]
  • Several coumarin derivatives[43] and #C19*[29] (see 3d model)
  • Phenylcoumarins, extremely subtype selective[44] and further analogs[45][46][47] (see 3d model)
  • Chromone-3-phenylcarboxamides[48]
  • Isatins[49]
  • Phthalimides[50]
  • 8-Benzyloxycaffeines[51][52] and CSC analogs[53]
  • (E,E)-8-(4-phenylbutadien-1-yl)caffeines,[54] with A2A antagonistic component
  • Indazole- and Indole-5-carboxamides[55]

Irreversible (covalent)

See also


  1. GRCh38: Ensembl release 89: ENSG00000069535 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000040147 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "Entrez Gene: MAOB monoamine oxidase B".
  6. Edmondson DE, Binda C, Mattevi A (August 2007). "Structural insights into the mechanism of amine oxidation by monoamine oxidases A and B". Arch. Biochem. Biophys. 464 (2): 269–76. doi:10.1016/ PMC 1993809. PMID 17573034.
  7. Youdim MB, Weinstock M (January 2004). "Therapeutic applications of selective and non-selective inhibitors of monoamine oxidase A and B that do not cause significant tyramine potentiation". Neurotoxicology. 25 (1–2): 243–50. doi:10.1016/S0161-813X(03)00103-7. PMID 14697899.
  8. Binda C, Hubálek F, Li M, Herzig Y, Sterling J, Edmondson DE, Mattevi A (March 2004). "Crystal structures of monoamine oxidase B in complex with four inhibitors of the N-propargylaminoindan class". J. Med. Chem. 47 (7): 1767–74. doi:10.1021/jm031087c. PMID 15027868.
  9. Nolen WA, Hoencamp E, Bouvy PF, Haffmans PM (1993). "Reversible monoamine oxidase-A inhibitors in resistant major depression". Clin Neuropharmacol. 16 (Suppl 2): S69–76. PMID 8313400.
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  11. Saura J, Luque JM, Cesura AM, Da Prada M, Chan-Palay V, Huber G, Löffler J, Richards JG (September 1994). "Increased monoamine oxidase B activity in plaque-associated astrocytes of Alzheimer brains revealed by quantitative enzyme radioautography". Neuroscience. 62 (1): 15–30. doi:10.1016/0306-4522(94)90311-5. PMID 7816197.
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  19. Grimsby J, Toth M, Chen K, Kumazawa T, Klaidman L, Adams JD, Karoum F, Gal J, Shih JC (October 1997). "Increased stress response and beta-phenylethylamine in MAOB-deficient mice". Nature Genetics. 17 (2): 206–10. doi:10.1038/ng1097-206. PMID 9326944.
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  30. Carotti A, Carrieri A, Chimichi S, Boccalini M, Cosimelli B, Gnerre C, Carotti A, Carrupt PA, Testa B (December 2002). "Natural and synthetic geiparvarins are strong and selective MAO-B inhibitors. Synthesis and SAR studies". Bioorg. Med. Chem. Lett. 12 (24): 3551–5. doi:10.1016/S0960-894X(02)00798-9. PMID 12443774.
  31. Uebelhack R, Franke L, Schewe HJ (September 1998). "Inhibition of platelet MAO-B by kava pyrone-enriched extract from Piper methysticum Forster (kava-kava)". Pharmacopsychiatry. 31 (5): 187–92. doi:10.1055/s-2007-979325. PMID 9832350.
  32. Dhingra, Dinesh; Kumar, Vaibhav (1 August 2008). "Evidences for the involvement of monoaminergic and GABAergic systems in antidepressant-like activity of garlic extract in mice". Indian Journal of Pharmacology. 40 (4): 175–179. doi:10.4103/0253-7613.43165. ISSN 0253-7613. PMC 2792615. PMID 20040952.
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  34. compound #2d, Frédérick R, Dumont W, Ooms F, Aschenbach L, Van der Schyf CJ, Castagnoli N, Wouters J, Krief A (June 2006). "Synthesis, structural reassignment, and biological activity of type B MAO inhibitors based on the 5H-indeno[1,2-c]pyridazin-5-one core". J. Med. Chem. 49 (12): 3743–7. doi:10.1021/jm051091j. PMID 16759116.
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  38. compound # (R)-8b, Chimenti F, Secci D, Bolasco A, Chimenti P, Granese A, Carradori S, Yáñez M, Orallo F, Sanna ML, Gallinella B, Cirilli R (September 2010). "Synthesis, stereochemical separation, and biological evaluation of selective inhibitors of human MAO-B: 1-(4-arylthiazol-2-yl)-2-(3-methylcyclohexylidene)hydrazines". J. Med. Chem. 53 (17): 6516–20. doi:10.1021/jm100120s. PMID 20715818.
  39. compound #18, Chimenti F, Maccioni E, Secci D, Bolasco A, Chimenti P, Granese A, Befani O, Turini P, Alcaro S, Ortuso F, Cardia MC, Distinto S (February 2007). "Selective inhibitory activity against MAO and molecular modeling studies of 2-thiazolylhydrazone derivatives". J. Med. Chem. 50 (4): 707–12. doi:10.1021/jm060869d. PMID 17253676.
  40. compound #3g, Chimenti F, Fioravanti R, Bolasco A, Manna F, Chimenti P, Secci D, Befani O, Turini P, Ortuso F, Alcaro S (February 2007). "Monoamine oxidase isoform-dependent tautomeric influence in the recognition of 3,5-diaryl pyrazole inhibitors". J. Med. Chem. 50 (3): 425–8. doi:10.1021/jm060868l. PMID 17266193.
  41. compound #(S)-1, 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 (November 2005). "Synthesis, molecular modeling studies, and selective inhibitory activity against monoamine oxidase of 1-thiocarbamoyl-3,5-diaryl-4,5-dihydro-(1H)- pyrazole derivatives". J. Med. Chem. 48 (23): 7113–22. doi:10.1021/jm040903t. PMID 16279769.
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  43. compound #41, Catto M, Nicolotti O, Leonetti F, Carotti A, Favia AD, Soto-Otero R, Méndez-Alvarez E, Carotti A (2006). "Structural insights into monoamine oxidase inhibitory potency and selectivity of 7-substituted coumarins from ligand- and target-based approaches". Journal of Medicinal Chemistry. 49 (16): 4912–25. doi:10.1021/jm060183l. PMID 16884303.
  44. compound #2, Matos MJ, Vazquez-Rodriguez S, Uriarte E, Santana L, Viña D (July 2011). "MAO inhibitory activity modulation: 3-Phenylcoumarins versus 3-benzoylcoumarins". Bioorg. Med. Chem. Lett. 21 (14): 4224–7. doi:10.1016/j.bmcl.2011.05.074. PMID 21684743.
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  48. compound #9, #12, Gaspar A, Reis J, Fonseca A, Milhazes N, Viña D, Uriarte E, Borges F (January 2011). "Chromone 3-phenylcarboxamides as potent and selective MAO-B inhibitors". Bioorg. Med. Chem. Lett. 21 (2): 707–9. doi:10.1016/j.bmcl.2010.11.128. PMID 21194943.
  49. compound #9i, Manley-King CI, Bergh JJ, Petzer JP (January 2011). "Inhibition of monoamine oxidase by selected C5- and C6-substituted isatin analogues". Bioorg. Med. Chem. 19 (1): 261–74. doi:10.1016/j.bmc.2010.11.028. PMID 21134756.
  50. compound #5c, Manley-King CI, Bergh JJ, Petzer JP (August 2011). "Inhibition of monoamine oxidase by C5-substituted phthalimide analogues". Bioorg. Med. Chem. 19 (16): 4829–40. doi:10.1016/j.bmc.2011.06.070. PMID 21778064.
  51. Strydom B, Bergh JJ, Petzer JP (August 2011). "8-Aryl- and alkyloxycaffeine analogues as inhibitors of monoamine oxidase". Eur J Med Chem. 46 (8): 3474–85. doi:10.1016/j.ejmech.2011.05.014. PMID 21621312.
  52. Strydom B, Malan SF, Castagnoli N, Bergh JJ, Petzer JP (February 2010). "Inhibition of monoamine oxidase by 8-benzyloxycaffeine analogues". Bioorg. Med. Chem. 18 (3): 1018–28. doi:10.1016/j.bmc.2009.12.064. PMID 20093036.
  53. Vlok N, Malan SF, Castagnoli N, Bergh JJ, Petzer JP (May 2006). "Inhibition of monoamine oxidase B by analogues of the adenosine A2A receptor antagonist (E)-8-(3-chlorostyryl)caffeine (CSC)". Bioorg. Med. Chem. 14 (10): 3512–21. doi:10.1016/j.bmc.2006.01.011. PMID 16442801.
  54. Pretorius J, Malan SF, Castagnoli N, Bergh JJ, Petzer JP (September 2008). "Dual inhibition of monoamine oxidase B and antagonism of the adenosine A(2A) receptor by (E,E)-8-(4-phenylbutadien-1-yl)caffeine analogues". Bioorganic & Medicinal Chemistry. 16 (18): 8676–84. doi:10.1016/j.bmc.2008.07.088. PMID 18723354.
  55. Tzvetkov; et al. (23 June 2014). "Indazole- and Indole-5-carboxamides: Selective and Reversible Monoamine Oxidase B Inhibitors with Subnanomolar Potency". Journal of Medicinal Chemistry. 57 (15): 6679–6703. doi:10.1021/jm500729a. PMID 24955776.
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