Skip to main content

Advertisement

SpringerLink
Log in

Kinetics, mechanism, and inhibition of monoamine oxidase

  • Neurology and Preclinical Neurological Studies - Review Article
  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Abstract

Monoamine oxidases (MAOs) catalyse the oxidation of neurotransmitter amines and a wide variety of primary, secondary and tertiary amine xenobiotics, including therapeutic drugs. While inhibition of MAO activity in the periphery removes protection from biogenic amines and so is undesirable, inhibition in the brain gives vital antidepressant and behavioural advantages that make MAO a major pharmaceutical target for inhibitor design. In neurodegenerative diseases, MAO inhibitors can help to maintain neurotransmitter levels, making it a common feature in novel multi-target combinations designed to combat Alzheimer’s disease, albeit not yet proven clinically. Vital information for inhibitor design comes from an understanding of the structure, mechanism, and kinetics of the catalyst. This review will summarize the kinetic behaviour of MAO A and B and the kinetic evaluation of reversible inhibitors that transiently decrease catalysis. Kinetic parameters and crystal structures have enabled computational approaches to ligand discovery and validation of hits by docking. Kinetics and a wide variety of substrates and inhibitors along with theoretical modelling have also contributed to proposed schemes for the still debated chemical mechanism of amine oxidation. However, most of the marketed MAO drugs are long-lasting irreversible inactivators. The mechanism of irreversible inhibition by hydrazine, cyclopropylamine, and propargylamine drugs will be discussed. The article finishes with some examples of the propargylamine moiety in multi-target ligand design to combat neurodegeneration.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Scheme 1
Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Scheme 2

Similar content being viewed by others

References

  • Abad E, Zenn RK, Kaestner J (2013) Reaction mechanism of monoamine oxidase from QM/MM calculations. J Phys Chem B 117(46):14238–14246. https://doi.org/10.1021/jp4061522

    Article  CAS  PubMed  Google Scholar 

  • Akyuz MA, Erdem SS (2013) Computational modeling of the direct hydride transfer mechanism for the MAO catalyzed oxidation of phenethylamine and benzylamine: ONIOM (QM/QM) calculations. J Neural Transm 120:937–945. https://doi.org/10.1007/s00702-013-1027-8

    Article  CAS  PubMed  Google Scholar 

  • Akyuz MA, Erdem SS, Edmondson DE (2007) The aromatic cage in the active site of monoamine oxidase B: effect on the structural and electronic properties of bound benzylamine and p-nitrobenzylamine. J Neural Transm 114(6):693–698

    CAS  PubMed  Google Scholar 

  • Apostolov R, Yonezawa Y, Standley DM, Kikugawa G, Takano Y, Nakamura H (2009) Membrane attachment facilitates ligand access to the active site in monoamine oxidase A. Biochemistry 48(25):5864–5873

    CAS  PubMed  Google Scholar 

  • Bach AWJ, Lan NC, Johnson DL, Abell CW, Bembenek ME, Kwan SW, Seeburg PH, Shih JC (1988) cDNA cloning of human-liver monoamine oxidase-A and oxidase-B—molecular basis of differences in enzymatic properties. PNAS USA 85(13):4934–4938

    CAS  PubMed  PubMed Central  Google Scholar 

  • Baker GB, Wong JT, Yeung JM, Coutts RT (1991) Effects of the antidepressant phenelzine on brain levels of gamma-aminobutyric acid (GABA). J Affect Disord 21(3):207–211

    CAS  PubMed  Google Scholar 

  • Basile L, Pappalardo M, Guccione S, Milardi D, Ramsay RR (2014) Computational comparison of imidazoline association with the 12 binding site in human monoamine oxidases. J Chem Inf Model 54(4):1200–1207

    CAS  PubMed  Google Scholar 

  • Bautista-Aguilera OM et al (2014a) Design, synthesis, pharmacological evaluation, QSAR analysis, molecular modeling and ADMET of novel donepezil-indolyl hybrids as multipotent cholinesterase/monoamine oxidase inhibitors for the potential treatment of Alzheimer’s disease. Eur J Med Chem 75:82–95. https://doi.org/10.1016/j.ejmech.2013.12.028

    Article  CAS  PubMed  Google Scholar 

  • Bautista-Aguilera OM et al (2014b) N-Methyl-N-((1-methyl-5-(3-(1-(2-methylbenzyl)piperidin-4yl)propoxy)-1H- indol-2-yl)methyl)prop-2-yn-1-amine, a new cholinesterase and monoamine oxidase dual inhibitor. J Med Chem 57(24):10455–10463. https://doi.org/10.1021/jm501501a

    Article  CAS  PubMed  Google Scholar 

  • Bautista-Aguilera O et al (2017) Multitarget-directed ligands combining cholinesterase and monoamine oxidase Inhibition with H3R antagonism for neurodegenerative diseases. Angew Chem 56:12765–12769. https://doi.org/10.1002/anie.201706072

    Article  CAS  Google Scholar 

  • Binda C, Newton-Vinson P, Hubalek F, Edmondson DE, Mattevi A (2002) Structure of human monoamine oxidase B, a drug target for the treatment of neurological disorders. Nat Struct Biol 9(1):22–26

    CAS  PubMed  Google Scholar 

  • Binda C, Li M, Hubalek F, Restelli N, Edmondson DE, Mattevi A (2003) Insights into the mode of inhibition of human mitochondrial monoamine oxidase B from high-resolution crystal structures. Proc Natl Acad Sci USA 100(17):9750–9755

    CAS  PubMed  PubMed Central  Google Scholar 

  • Binda C, Hubalek F, Li M, Herzig Y, Sterling J, Edmondson DE, Mattevi A (2004) Crystal structures of monoamine oxidase B in complex with four inhibitors of the N-propargylaminoindan class. J Med Chem 47(7):1767–1774

    CAS  PubMed  Google Scholar 

  • Binda C, Hubalek F, Li M, Castagnoli N, Edmondson DE, Mattevi A (2006) Structure of the human mitochondrial monoamine oxidase B—new chemical implications for neuroprotectant drug design. Neurology 67(7):S5–S7

    CAS  PubMed  Google Scholar 

  • Binda C, Wang J, Pisani L, Caccia C, Carotti A, Salvati P, Edmondson DE, Mattevi A (2007) Structures of human monoamine oxidase B complexes with selective noncovalent inhibitors: safinamide and coumarin analogs. J Med Chem 50(23):5848–5852

    CAS  PubMed  Google Scholar 

  • Binda C, Wang J, Li M, Hubalek F, Mattevi A, Edmondson DE (2008) Structural and mechanistic studies of arylalkylhydrazine inhibition of human monoamine oxidases A and B. Biochemistry 47(20):5616–5625

    CAS  PubMed  Google Scholar 

  • Binda C et al (2010) Biochemical, structural, and biological evaluation of tranylcypromine derivatives as inhibitors of histone demethylases LSD1 and LSD2. J Am Chem Soc 132(19):6827–6833

    CAS  PubMed  Google Scholar 

  • Binda C, Mattevi A, Edmondson DE (2011) Structural properties of human monoamine oxidases A AND B. In: Youdim MBH, Riederer P (eds) Monoamine oxidases and their inhibitors. Int Rev Neurobiol 100:1–11. https://doi.org/10.1016/b978-0-12-386467-3.00001-7

    Google Scholar 

  • Binda C, Aldeco M, Geldenhuys WJ, Tortorici M, Mattevi A, Edmondson DE (2012) Molecular insights into human monoamine oxidase B inhibition by the glitazone antidiabetes drugs. Med Chem Lett 3(1):39–42

    CAS  Google Scholar 

  • Bocchinfuso R, Robinson JB (1999) The stereoselectivity of inhibition of rat liver mitochondrial MAO-A and MAO-B by the enantiomers of 2-phenylpropylamine and their derivatives. Eur J Med Chem 34(4):293–300. https://doi.org/10.1016/S0223-5234(99)80080-4

    Article  CAS  Google Scholar 

  • Bolea I, Juarez-Jimenez J, de los Rios C, Chioua M, Pouplana R, Luque FJ, Unzeta M, Marco-Contelles J, Samadi A (2011) Synthesis, biological evaluation, and molecular modeling of donepezil and N-(5-(benzyloxy)-1-methyl-1H-indol-2-yl)methyl-N-methylprop-2-yn-1-ami ne hybrids as new multipotent cholinesterase/monoamine oxidase inhibitors for the treatment of Alzheimer’s disease. J Med Chem 54(24):8251–8270. https://doi.org/10.1021/jm200853t

    Article  CAS  PubMed  Google Scholar 

  • Bonnet U (2002) Moclobemide: evolution, pharmacodynamic, and pharmacokinetic properties. CNS Drug REV 8(3):283–308

    CAS  PubMed  PubMed Central  Google Scholar 

  • Borroni E et al (2017) Sembragiline: a novel, selective monoamine oxidase type B inhibitor for the treatment of Alzheimer’s disease. J Pharmacol Exp Ther 362(3):413–423. https://doi.org/10.1124/jpet.117.241653

    Article  CAS  PubMed  Google Scholar 

  • Borstnar R, Repic M, Krzan M, Mavri J, Vianello R (2011) Irreversible inhibition of monoamine oxidase B by the antiparkinsonian medicines rasagiline and selegiline: a computational study. Eur J Org Chem 32:6419–6433. https://doi.org/10.1002/ejoc.201100873

    Article  CAS  Google Scholar 

  • Bortolato M, Shih JC (2011) Behavioral outcomes of monoamine oxidase deficiency: Preclinical and clinical evidence. In: Youdim MBH, Riederer P (eds) Monoamine oxidases and their inhibitors. Int Rev Neurobiol 100:13–42. https://doi.org/10.1016/b978-0-12-386467-3.00002-9

    Google Scholar 

  • Caccia C, Maj R, Calabresi M, Maestroni S, Faravelli L, Curatolo L, Salvati P, Fariello RG (2006) Safinamide—from molecular targets to a new anti-Parkinson drug. Neurology 67(7):S18–S23

    CAS  PubMed  Google Scholar 

  • Cakir K, Erdem SS, Atalay VE (2016) ONIOM calculations on serotonin degradation by monoamine oxidase B: insight into the oxidation mechanism and covalent reversible inhibition. Org Biomol Chem 14(39):9239–9252. https://doi.org/10.1039/c6ob01175f

    Article  CAS  PubMed  Google Scholar 

  • Carradori S, Silvestri R (2015) New frontiers in selective human MAO-B inhibitors. J Med Chem 58(17):6717–6732. https://doi.org/10.1021/jm501690r

    Article  CAS  PubMed  Google Scholar 

  • Cesura AM, Pletscher A (1992) The new generation of monoamine oxidase inhibitors. Prog Drug Res (Fortschritte der Arzneimittelforschung Progres des recherches pharmaceutiques) 38:171–297

    CAS  Google Scholar 

  • Chajkowski-Scarry S, Rimoldi JM (2014) Monoamine oxidase A and B substrates: probing the pathway for drug development. Future Med Chem 6(6):697–717. https://doi.org/10.4155/fmc.14.23

    Article  CAS  PubMed  Google Scholar 

  • Chiuccariello L et al (2016) Monoamine oxidase-A occupancy by moclobemide and phenelzine: implications for the development of monoamine oxidase inhibitors. Int J Neuropsychopharmacol. https://doi.org/10.1093/ijnp/pyv078

    Article  Google Scholar 

  • Copeland RA, Lombardo D, Giannaras J, Decicco CP (1995) Estimating K-i values for tight-binding inhibitors from dose–response plots. Bioorg Med Chem Lett 5(17):1947–1952. https://doi.org/10.1016/0960-894x(95)00330-v

    Article  CAS  Google Scholar 

  • Cruz F, Edmondson DE (2007) Kinetic properties of recombinant MAO-A on incorporation into phospholipid nanodisks. J Neural Transm 114(6):699–702

    CAS  PubMed  Google Scholar 

  • Culhane JC, Wang D, Yen PM, Cole PA (2010) Comparative analysis of small molecules and histone substrate analogues as LSD1 lysine demethylase inhibitors. J Am Chem Soc 132(9):3164–3176. https://doi.org/10.1021/ja909996p

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Da Prada M et al (1990) From moclobemide to Ro 19-6327 and Ro 41-1049: the development of a new class of reversible, selective MAO-A and MAO-B inhibitors. J Neural Transm 29:279–292

    Google Scholar 

  • De Colibus L, Li M, Binda C, Lustig A, Edmondson DE, Mattevi A (2005) Three-dimensional structure of human monoamine oxidase A (MAO A): relation to the structures of rat MAO A and human MAO B. PNAS USA 102(36):12684–12689

    PubMed  PubMed Central  Google Scholar 

  • Delport A, Harvey BH, Petzer A, Petzer JP (2017) The monoamine oxidase inhibition properties of selected structural analogues of methylene blue. Toxicol Appl Pharmacol 325:1–8. https://doi.org/10.1016/j.taap.2017.03.026

    Article  CAS  PubMed  Google Scholar 

  • Desideri N, Proietti Monaco L, Fioravanti R, Biava M, Yanez M, Alcaro S, Ortuso F (2016) (E)-3-Heteroarylidenechroman-4-ones as potent and selective monoamine oxidase-B inhibitors. Eur J Med Chem 117:292–300. https://doi.org/10.1016/j.ejmech.2016.03.081

    Article  CAS  PubMed  Google Scholar 

  • Dorris RL (1982) A simple method for screening monoamine oxidase (MAO) inhibitory drugs for type preference. J Pharmacol Methods 7(2):133–137

    CAS  PubMed  Google Scholar 

  • Dunn RV, Marshall KR, Munro AW, Scrutton NS (2008) The pH dependence of kinetic isotope effects in monoamine oxidase A indicates stabilization of the neutral amine in the enzyme-substrate complex. FEBS J 275(15):3850–3858. https://doi.org/10.1111/j.1742-4658.2008.06532.x

    Article  CAS  PubMed  Google Scholar 

  • Dunn RV, Munro AW, Turner NJ, Rigby SEJ, Scrutton NS (2010) Tyrosyl radical formation and propagation in flavin dependent monoamine oxidases. ChemBioChem 11(9):1228–1231

    CAS  PubMed  Google Scholar 

  • Edmondson DE, Newton-Vinson P (2001) The covalent FAD of monoamine oxidase: structural and functional role and mechanism of the flavinylation reaction. Antioxid Redox Signal 3(5):789–806

    CAS  PubMed  Google Scholar 

  • Edmondson DE, Mattevi A, Binda C, Li M, Hubalek F (2004) Structure and mechanism of monoamine oxidase. Curr Med Chem 11(15):1983–1993

    CAS  PubMed  Google Scholar 

  • Edmondson DE, Binda C, Mattevi A (2007) Structural insights into the mechanism of amine oxidation by monoamine oxidases A and B. Arch Biochem Biophys 464(2):269–276

    CAS  PubMed  PubMed Central  Google Scholar 

  • Edmondson DE, Binda C, Wang J, Upadhyay AK, Mattevi A (2009) Molecular and mechanistic properties of the membrane-bound mitochondrial monoamine oxidases. Biochemistry 48(20):4220–4230

    CAS  PubMed  Google Scholar 

  • Efange SM, Boudreau RJ (1991) Molecular determinants in the bioactivation of the dopaminergic neurotoxin N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). J Comput Aided Mol Des 5(5):405–417

    CAS  PubMed  Google Scholar 

  • Efange SMN, Michelson RH, Tan AK, Krueger MJ, Singer TP (1993) Molecular-size and flexibility as determinants of selectivity in the oxidation of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine analogs of monoamine oxidase-A and oxidase-B. J Med Chem 36(9):1278–1283

    CAS  PubMed  Google Scholar 

  • Esteban G, Allan J, Samadi A, Mattevi A, Unzeta M, Marco-Contelles J, Binda C, Ramsay RR (2014) Kinetic and structural analysis of the irreversible inhibition of human monoamine oxidases by ASS234, a multi-target compound designed for use in Alzheimer’s disease. Biochem Biophys Acta 1844(6):1104–1110

    CAS  PubMed  Google Scholar 

  • Finberg J, Rabey J (2016) Inhibitors of MAO-A and MAO-B in psychiatry and neurology. Front Pharmacol 7:340. https://doi.org/10.3389/fphar.2016.00340

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fisar Z (2016) Drugs related to monoamine oxidase activity. Prog Neuro Psychopharmacol Biol Psychiatry 69:112–124. https://doi.org/10.1016/j.pnpbp.2016.02.012

    Article  CAS  Google Scholar 

  • Fitzpatrick PF (2010) Oxidation of amines by flavoproteins. Arch Biochem Biophys 493(1):13–25

    CAS  PubMed  Google Scholar 

  • Fitzpatrick PF, Villafranca JJ (1986) The mechanism of inactivation of dopamine beta-hydroxylase by hydrazines. J Biol Chem 261(10):4510–4518

    CAS  PubMed  Google Scholar 

  • Fowler CJ, Oreland L (1980) The nature of the substrate-selective interaction between rat liver mitochondrial monoamine-oxidase and oxygen. Biochem Pharmacol 29(16):2225–2233

    CAS  PubMed  Google Scholar 

  • Fowler CJ, Mantle TJ, Tipton KF (1982) The nature of the inhibition of rat-liver monoamine-oxidase type-A and type-B by the acetylenic inhibitors clorgyline, l-deprenyl and pargyline. Biochem Pharmacol 31(22):3555–3561

    CAS  PubMed  Google Scholar 

  • Fowler JS, Logan J, Shumay E, Alia-Klein N, Wang G-J, Volkow ND (2015) Monoamine oxidase: radiotracer chemistry and human studies. J Label Compd Radiopharm 58(3):51–64. https://doi.org/10.1002/jlcr.3247

    Article  CAS  Google Scholar 

  • Fraaije MW, Mattevi A (2000) Flavoenzymes: diverse catalysts with recurrent features. Trends Biochem Sci 25(3):126–132

    CAS  PubMed  Google Scholar 

  • Fuentes JA, Oleshansky MA, Neff NH (1976) Comparison of apparent antidepressant activity of (−) and (+) tranylcypromine in an animal-model. Biochem Pharmacol 25(7):801–804. https://doi.org/10.1016/0006-2952(76)90150-7

    Article  CAS  PubMed  Google Scholar 

  • Garcia-Miralles M, Ooi J, Ferrari Bardile C, Tan LJ, George M, Drum CL, Lin RY, Hayden MR, Pouladi MA (2016) Treatment with the MAO-A inhibitor clorgyline elevates monoamine neurotransmitter levels and improves affective phenotypes in a mouse model of Huntington disease. Exp Neurol 278:4–10. https://doi.org/10.1016/j.expneurol.2016.01.019

    Article  CAS  PubMed  Google Scholar 

  • Gartner B, Hemmerich P, Zeller EA (1976) Structure of flavin adducts with acetylenic substrates—chemistry of monoamine-oxidase and lactate oxidase Inhibition. Eur J Biochem 63(1):211–221

    CAS  PubMed  Google Scholar 

  • Geha RM, Chen K, Shih JC (2000) Phe(208) and Ile(199) in human monoamine oxidase A and B do not determine substrate and inhibitor specificities as in rat. J Neurochem 75(3):1304–1309

    CAS  PubMed  Google Scholar 

  • Geha RM, Rebrin I, Chen K, Shih JC (2001) Substrate and inhibitor specificities for human monoamine oxidase A and B are influenced by a single amino acid. J Biol Chem 276(13):9877–9882

    CAS  PubMed  Google Scholar 

  • Griebel G, Curet O, Perrault G, Sanger DJ (1998) Behavioral effects of phenelzine in an experimental model for screening anxiolytic and anti-panic drugs: correlation with changes in monoamine-oxidase activity and monoamine levels. Neuropharmacol 37(7):927–935. https://doi.org/10.1016/S0028-3908(98)00077-X

    Article  CAS  Google Scholar 

  • Guzior N, Wieckowska A, Panek D, Malawska B (2015) Recent development of multifunctional agents as potential drug candidates for the treatment of Alzheimer’s disease. Curr Med Chem 22(3):373–404

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hanzlik RP, Tullman RH (1982) Suicidal Inactivation of cytochrome-P-450 by cyclopropylamines—evidence for cation-radical intermediates. J Am Chem Soc 104(7):2048–2050

    CAS  Google Scholar 

  • Heal DJ, Smith SL, Gosden J, Nutt DJ (2013) Amphetamine, past and present—a pharmacological and clinical perspective. J Psychopharmacol (Oxford, England) 27(6):479–496. https://doi.org/10.1177/0269881113482532

    Article  CAS  Google Scholar 

  • Holt A, Palcic MM (2006) A peroxidase-coupled continuous absorbance plate-reader assay for flavin monoamine oxidases, copper-containing amine oxidases and related enzymes. Nat Protoc 1:2498–2505

    CAS  PubMed  Google Scholar 

  • Hroch L et al (2017) Synthesis and evaluation of frentizole-based indolyl thiourea analogues as MAO/ABAD inhibitors for Alzheimer’s disease treatment. Bioorg Med Chem 25(3):1143–1152. https://doi.org/10.1016/j.bmc.2016.12.029

    Article  CAS  PubMed  Google Scholar 

  • Hruschka S, Rosen TC, Yoshida S, Kirk KL, Froehlich R, Wibbeling B, Haufe G (2008) Fluorinated phenylcyclopropylamines. Part 5: effects of electron-withdrawing or -donating aryl substituents on the inhibition of monoamine oxidases A and B by 2-aryl-2-fluoro-cyclopropylamines. Bioorg Med Chem 16(15):7148–7166

    CAS  PubMed  PubMed Central  Google Scholar 

  • Huang P-KC, Kosower EM (1967) Properties of phenyldiimide. J Am Chem Soc 89(15):3910–3911. https://doi.org/10.1021/ja00991a047

    Article  CAS  Google Scholar 

  • Hubalek F, Binda C, Li M, Herzig Y, Sterling J, Youdim MB, Mattevi A, Edmondson DE (2004) Inactivation of purified human recombinant monoamine oxidases A and B by rasagiline and its analogues. J Med Chem 47(7):1760–1766. https://doi.org/10.1021/jm0310885

    Article  CAS  PubMed  Google Scholar 

  • Hubalek F, Binda C, Khalil A, Li M, Mattevi A, Castagnoli N, Edmondson DE (2005) Demonstration of isoleucine 199 as a structural determinant for the selective inhibition of human monoamine oxidase B by specific reversible inhibitors. J Biol Chem 280(16):15761–15766

    CAS  PubMed  Google Scholar 

  • Husain M, Edmondson DE, Singer TP (1982) Kinetic-studies on the catalytic mechanism of liver monoamine oxidase. Biochemistry 21(3):595–600

    CAS  PubMed  Google Scholar 

  • Hutson PH, Tarazi FI, Madhoo M, Slawecki C, Patkar AA (2014) Preclinical pharmacology of amphetamine: implications for the treatment of neuropsychiatric disorders. Pharmacol Ther 143(3):253–264. https://doi.org/10.1016/j.pharmthera.2014.03.005

    Article  CAS  PubMed  Google Scholar 

  • Hynson RMG, Wouters J, Ramsay RR (2003) Monoamine oxidase A inhibitory potency and flavin perturbation are influenced by different aspects of pirlindole inhibitor structure. Biochem Pharmacol 65(11):1867–1874

    CAS  PubMed  Google Scholar 

  • Hynson R, Kelly S, Price N, Ramsay R (2004) Conformational changes in monoamine oxidase A in response to ligand binding or reduction. Biochem Biophys Acta 1672(1):60–66. https://doi.org/10.1016/j.bbagen.2004.02.011

    Article  CAS  PubMed  Google Scholar 

  • Jones T, Balsa D, Unzeta M, Ramsay R (2007) Variations in activity and inhibition with pH: the protonated amine is the substrate for monoamine oxidase, but uncharged inhibitors bind better. J Neural Transm 114(6):707–712. https://doi.org/10.1007/s00702-007-0675-y

    Article  CAS  PubMed  Google Scholar 

  • Jonsson T, Edmondson DE, Klinman JP (1994) Hydrogen tunneling in the flavoenzyme monoamine-oxidase-B. Biochemistry 33(49):14871–14878

    CAS  PubMed  Google Scholar 

  • Joubert J, Foka GB, Repsold BP, Oliver DW, Kapp E, Malan SF (2017) Synthesis and evaluation of 7-substituted coumarin derivatives as multimodal monoamine oxidase-B and cholinesterase inhibitors for the treatment of Alzheimer’s disease. Eur J Med Chem 125:853–864. https://doi.org/10.1016/j.ejmech.2016.09.041

    Article  CAS  PubMed  Google Scholar 

  • Juarez-Jimenez J, Mendes E, Galdeano C, Martins C, Silva D, Marco-Contelles J, Carreiras M, Luque F, Ramsay R (2014) Exploring the structural basis of the selective inhibition of monoamine oxidase A by dicarbonitrile aminoheterocycles: role of Asn181 and Ile335 validated by spectroscopic and computational studies. Biochem Biophys Acta 1844(2):389–397. https://doi.org/10.1016/j.bbapap.2013.11.003

    Article  CAS  PubMed  Google Scholar 

  • Juárez-Jiménez J, Mendes E, Galdeano C, Martins C, Silva DB, Marco-Contelles J, Carreiras MdC, Luque FJ, Ramsay RR (2014) Exploring the structural basis of the selective inhibition of monoamine oxidase A by dicarbonitrile aminoheterocycles: role of Asn181 and Ile335 validated by spectroscopic and computational studies. Biochim Biophys Acta (Proteins Proteom) 1844:389–397. https://doi.org/10.1016/j.bbapap.2014.03.006

    Article  CAS  Google Scholar 

  • Kacar B, Edmondson D (2006) Studies on the role of lysine-296 in human mitochondrial monoamine oxidase B catalysis. FASEB J 20(4):A478

    Google Scholar 

  • Kalgutkar AS, Castagnoli N, Testa B (1995) Selective inhibitors of monoamine-oxidase (MAO-A and MAO-B) as probes of its catalytic site and mechanism. Med Res Rev 15(4):325–388

    CAS  PubMed  Google Scholar 

  • Kalgutkar AS, Dalvie DK, Castagnoli N, Taylor TJ (2001) Interactions of nitrogen-containing xenobiotics with monoamine oxidase (MAO) isozymes A and B: sAR studies on MAO substrates and inhibitors. Chem Res Toxicol 14(9):1139–1162

    CAS  PubMed  Google Scholar 

  • Kalir A, Sabbagh A, Youdim MB (1981) Selective acetylenic ‘suicide’ and reversible inhibitors of monoamine oxidase types A and B. Br J Pharmacol 73(1):55–64

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kay CWM, El Mkami H, Molla G, Pollegioni L, Ramsay RR (2007) Characterization of the covalently bound anionic flavin radical in monoamine oxidase a by electron paramagnetic resonance. J Am Chem Soc 129(51):16091–16097

    CAS  PubMed  Google Scholar 

  • Kearney EB, Salach JI, Walker WH, Seng RL, Kenney W, Zeszotek E, Singer TP (1971) Covalently-bound flavin of hepatic monoamine oxidase.1. Isolation and sequence of a flavin peptide and evidence for binding at 8 alpha-position. Eur J Biochem 24(2):321–327

    CAS  PubMed  Google Scholar 

  • Khan MNA, Suzuki T, Miyata N (2013) An overview of phenylcyclopropylamine derivatives: biochemical and biological significance and recent developments. Med Res Rev 33(4):873–910

    CAS  PubMed  Google Scholar 

  • Kim J-M, Hoegy SE, Mariano PS (1995) Flavin chemical models for monoamine oxidase inactivation by cyclopropylamines, alpha-silylamines, and hydrazines. J Am Chem Soc 117(1):100–105. https://doi.org/10.1021/ja00106a012

    Article  CAS  Google Scholar 

  • Kim H, Sablin S, Ramsay R (1997) Inhibition of monoamine oxidase A by beta-carboline derivatives. Arch Biochem Biophys 337(1):137–142. https://doi.org/10.1006/abbi.1996.9771

    Article  CAS  PubMed  Google Scholar 

  • Kim D, Baik SH, Kang S, Cho SW, Bae J, Cha MY, Sailor MJ, Mook-Jung I, Ahn KH (2016) Close correlation of monoamine oxidase activity with progress of alzheimer’s disease in mice, observed by in vivo two-photon imaging. ACS Cent Sci 2(12):967–975. https://doi.org/10.1021/acscentsci.6b00309

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kitz R, Wilson IB (1962) Esters of methanesulfonic acid as irreversible inhibitors of acetylcholinesterase. J Biol Chem 237:3245–3249

    CAS  PubMed  Google Scholar 

  • Kosower EM (1971) Monosubstituted diazenes (diimides). Surprising intermediates. Acc Chem Res 4(6):193–198. https://doi.org/10.1021/ar50042a001

    Article  CAS  Google Scholar 

  • Kupershmidt L, Amit T, Bar-Am O, Youdim MBH, Weinreb O (2012) The novel multi-target iron chelating-radical scavenging compound M30 possesses beneficial effects on major hallmarks of Alzheimer’s disease. Antioxid Redox Signal 17(6):860–877. https://doi.org/10.1089/ars.2011.4279

    Article  CAS  PubMed  Google Scholar 

  • Leonardi ET, Azmitia EC (1994) MDMA (ecstasy) inhibition of MAO type A and type B: comparisons with fenfluramine and fluoxetine (Prozac). Neuropsychopharmacol 10(4):231–238. https://doi.org/10.1038/npp.1994.26

    Article  CAS  Google Scholar 

  • Li M, Binda C, Mattevi A, Edmondson DE (2006) Functional role of the “aromatic cage” in human monoamine oxidase B: structures and catalytic properties of Tyr435 mutant proteins. Biochemistry 45(15):4775–4784

    CAS  PubMed  Google Scholar 

  • Li XF, Yu JJ, Zhu Q, Qian LH, Li L, Zheng YG, Yao SQ (2014a) Visualization of monoamine oxidases in living cells using “Turn-ON” fluorescence resonance energy transfer probes. Analyst 139(23):6092–6095. https://doi.org/10.1039/c4an01195c

    Article  CAS  PubMed  Google Scholar 

  • Li XF, Zhang HT, Xie YS, Hu Y, Sun HY, Zhu Q (2014b) Fluorescent probes for detecting monoamine oxidase activity and cell imaging. Org Biomol Chem 12(13):2033–2036. https://doi.org/10.1039/c3ob42326c

    Article  CAS  PubMed  Google Scholar 

  • Li LL, Li K, Liu YH, Xu HR, Yu XQ (2016) Red emission fluorescent probes for visualization of monoamine oxidase in living cells. Sci Rep. https://doi.org/10.1038/srep31217

    Article  PubMed  PubMed Central  Google Scholar 

  • Lizcano JM, Fernandez de Arriba A, Tipton KF, Unzeta M (1996) Inhibition of bovine lung semicarbazide-sensitive amine oxidase (SSAO) by some hydrazine derivatives. Biochem Pharmacol 52(2):187–195

    CAS  PubMed  Google Scholar 

  • Ma JC, Yoshimura M, Yamashita E, Nakagawa A, Ito A, Tsukihara T (2004) Structure of rat monoamine oxidase A and its specific recognitions for substrates and inhibitors. J Mol Biol 338(1):103–114

    CAS  PubMed  Google Scholar 

  • MacMillar S, Edmondson DE, Matsson O (2011) Nitrogen kinetic isotope effects for the monoamine oxidase B-catalyzed oxidation of benzylamine and (1,1-(2)H(2))benzylamine: nitrogen rehybridization and CH bond cleavage are not concerted. J Am Chem Soc 133(32):12319–12321

    CAS  PubMed  Google Scholar 

  • Magyar K, Palfi M, Jenei V, Szoko E (2006) Deprenyl: from chemical synthesis to neuroprotection. J Neural Transm Suppl 71:143–156

    CAS  Google Scholar 

  • Malcomson T, Yelekci K, Borrello MT, Ganesan A, Semina E, De Kimpe N, Mangelinckx S, Ramsay RR (2015) cis-Cyclopropylamines as mechanism-based inhibitors of monoamine oxidases. FEBS J 282(16):3190–3198. https://doi.org/10.1111/febs.13260

    Article  CAS  PubMed  Google Scholar 

  • Mangiatordi GF et al (2017) A rational approach to elucidate human monoamine oxidase molecular selectivity. Eur J Pharm Sci 101:90–99. https://doi.org/10.1016/j.ejps.2017.02.008

    Article  CAS  PubMed  Google Scholar 

  • Mantle TJ, Tipton KF, Garrett NJ (1976) Inhibition of monoamine oxidase by amphetamine and related compounds. Biochem Pharmacol 25(18):2073–2077

    CAS  PubMed  Google Scholar 

  • Marco-Contelles J, Unzeta M, Bolea I, Esteban G, Ramsay RR, Romero A, Martnez-Murillo R, Carreiras MC, Ismaili L (2016) ASS234, as a new multi-target directed propargylamine for Alzheimer’s disease therapy. Front Neurosci. https://doi.org/10.3389/fnins.2016.00294

    Article  PubMed  PubMed Central  Google Scholar 

  • Matsumoto T, Suzuki O, Furuta T, Asai M, Kurokawa Y, Nimura Y, Katsumata Y, Takahashi I (1985) A sensitive fluorometric assay for serum monoamine-oxidase with kynuramine as substrate. Clin Biochem 18(2):126–129

    CAS  PubMed  Google Scholar 

  • Maycock AL, Abeles RH, Salach JI, Singer TP (1976a) The action of acetylenic inhibitors on mitochondrial monoamine oxidase: structure of the flavin site in the inhibited enzyme. In: Bernheim MLC (ed) Monoamine oxidase and its inhibition, Ciba foundation symposium, vol 439. Wiley, pp 33–47. https://doi.org/10.1002/9780470720219.ch3

    Google Scholar 

  • Maycock AL, Abeles RH, Salach JI, Singer TP (1976b) Structure of covalent adduct formed by interaction of 3-dimethylamino-1-propyne and flavin of mitochondrial amine oxidase. Biochemistry 15(1):114–125

    CAS  PubMed  Google Scholar 

  • Mazouz F, Gueddari S, Burstein C, Mansuy D, Milcent R (1993) 5- 4-(Benzyloxy)phenyl -1,3,4-oxadiazol-2(3h)-one derivatives and related analogs—new reversible, highly potent, and selective monoamine-oxidase type-B inhibitors. J Med Chem 36(9):1157–1167

    CAS  PubMed  Google Scholar 

  • McCoubrey A (1957) Inhibition of monoamine oxidase by 1-phenylethylamines. Biochem Pharmacol 2(4):264–269. https://doi.org/10.1016/0006-2952(59)90039-5

    Article  Google Scholar 

  • McDonald AG, Tipton KF (2012) Enzymes: irreversible inhibition. In: eLS. John Wiley & Sons Ltd, Chichester. https://doi.org/10.1002/9780470015902.a0000601.pub2

  • McDonald GR, Olivieri A, Ramsay RR, Holt A (2010) On the formation and nature of the imidazoline I(2) binding site on human monoamine oxidase-B. Pharmacol Res 62(6):475–488

    CAS  PubMed  Google Scholar 

  • Medvedev AE et al (1999) inhibition of monoamine oxidase by pirlindole analogues: 3D-QSAR analysis. Neurobiology 7(2):151–158

    CAS  PubMed  Google Scholar 

  • Mefford IN, Roth KA, Jurik SM, Collman V, McIntire S, Tolbert L, Barchas JD (1985) Epinephrine accumulation in rat brain after chronic administration of pargyline and LY 51641—comparison with other brain amines. Brain Res 339(2):342–345

    CAS  PubMed  Google Scholar 

  • Meiring L, Petzer JP, Petzer A (2013) Inhibition of monoamine oxidase by 3,4-dihydro-2(1H)-quinolinone derivatives. Bioorg Med Chem Lett 23(20):5498–5502. https://doi.org/10.1016/j.bmcl.2013.08.071

    Article  CAS  PubMed  Google Scholar 

  • Milczek EM, Binda C, Rovida S, Mattevi A, Edmondson DE (2011) The ‘gating’ residues Ile199 and Tyr326 in human monoamine oxidase B function in substrate and inhibitor recognition. FEBS J 278(24):4860–4869

    CAS  PubMed  PubMed Central  Google Scholar 

  • Miller JR, Edmondson DE (1999a) Influence of flavin analogue structure on the catalytic activities and flavinylation reactions of recombinant human liver monoamine oxidases A and B. J Biol Chem 274(33):23515–23525

    CAS  PubMed  Google Scholar 

  • Miller JR, Edmondson DE (1999b) Structure-activity relationships in the oxidation of para- substituted benzylamine analogues by recombinant human liver monoamine oxidase A. Biochemistry 38(41):13670–13683

    CAS  PubMed  Google Scholar 

  • Miller HH, Shore PA, Clarke DE (1980) In vivo monoamine oxidase inhibition by d-amphetamine. Biochem Pharmacol 29(10):1347–1354

    CAS  PubMed  Google Scholar 

  • Morrison JF (1969) Kinetics of reversible inhibition of enzyme-catalysed reactions by tight-binding inhibitors. Biochim Biophys Acta 185:269–286. https://doi.org/10.1016/0005-2744(69)90420-3

    Article  CAS  PubMed  Google Scholar 

  • Mure M et al (2005) Role of the interactions between the active site base and the substrate Schiff base in amine oxidase catalysis. Evidence from structural and spectroscopic studies of the 2-hydrazinopyridine adduct of Escherichia coli amine oxidase. Biochemistry 44(5):1568–1582. https://doi.org/10.1021/bi047988k

    Article  CAS  PubMed  Google Scholar 

  • Murphy DL, Donnelly CH, Richelson E, Fuller RW (1978) N-Substituted cyclopropylamines as inhibitors of MAO-A and MAO-B forms. Biochem Pharmacol 27(13):1767–1769

    CAS  PubMed  Google Scholar 

  • Murphy DL, Sunderland T, Garrick NA, Aulakh CS, Cohen RM (1987) Selective amine oxidase inhibitors: basic to clinical studies and back. In: Dahl ML, Gram LF, Potter LF (eds) Clinical pharmacology in psychiatry. Springer, Berlin, pp 135–146

    Google Scholar 

  • Nagy J, Kenney WC, Singer TP (1979) Reaction of phenylhydrazine with trimethylamine dehydrogenase and with free flavins. J Biol Chem 254(8):2684–2688

    CAS  PubMed  Google Scholar 

  • Nakai S, Yoneda F, Yamabe T, Fukui K (1999) Inhibition mechanism of flavin by deprenyl as an acetylenic irreversible inhibitor. Theor Chem Acc 102(1–6):147–160

    CAS  Google Scholar 

  • Nandigama RK, Edmondson DE (2000) Structure-activity relations in the oxidation of phenethylamine analogues by recombinant human liver monoamine oxidase A. Biochemistry 39(49):15258–15265

    CAS  PubMed  Google Scholar 

  • Naoi M, Maruyama W, Inaba-Hasegawa K, Akao Y (2011) Type A monoamine oxidase regulates life and death of neurons in neurodegeneration and neuroprotection. In: Monoamine oxidases and their inhibitors. Int Rev Neurobiol 100:85–106

  • Naoi M, Riederer P, Maruyama W (2016) Modulation of monoamine oxidase (MAO) expression in neuropsychiatric disorders: genetic and environmental factors involved in type A MAO expression. J Neural Transm 123(2):91–106. https://doi.org/10.1007/s00702-014-1362-4

    Article  CAS  PubMed  Google Scholar 

  • Newton-Vinson P, Hubalek F, Edmondson DE (2000) High-level expression of human liver monoamine oxidase B in Pichia pastoris. Protein Expr Purif 20(2):334–345

    CAS  PubMed  Google Scholar 

  • Nikolic K, Mavridis L, Djikic T, Vucicevic J, Agbaba D, Yelekci K, Mitchell JBO (2016) Drug design for CNS diseases: polypharmacological profiling of compounds using cheminformatic, 3D-QSAR and virtual screening methodologies. Front Neurosci. https://doi.org/10.3389/fnins.2016.00265

    Article  PubMed  PubMed Central  Google Scholar 

  • Niwa H, Umehara T (2017) Structural insight into inhibitors of flavin adenine dinucleotide-dependent lysine demethylases. Epigenetics 12(5):340–352. https://doi.org/10.1080/15592294.2017.1290032

    Article  PubMed  PubMed Central  Google Scholar 

  • Oanca G, Purg M, Mavri J, Shih JC, Stare J (2016) Insights into enzyme point mutation effect by molecular simulation: phenylethylamine oxidation catalyzed by monoamine oxidase A. Phys Chem Chem Phys 18(19):13346–13356. https://doi.org/10.1039/c6cp00098c

    Article  CAS  PubMed  Google Scholar 

  • Orru R, Aldeco M, Edmondson DE (2013) Do MAO A and MAO B utilize the same mechanism for the C–H bond cleavage step in catalysis? Evidence suggesting differing mechanisms. J Neural Transm 120(6):847–851. https://doi.org/10.1007/s00702-013-0991-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Paech C, Salach JI, Singer TP (1980) Suicide inactivation of monoamine-oxidase by trans-phenylcyclopropylamine. J Biol Chem 255(7):2700–2704

    CAS  PubMed  Google Scholar 

  • Parent MB, Master S, Kashlub S, Baker GB (2002) Effects of the antidepressant/antipanic drug phenelzine and its putative metabolite phenylethylidenehydrazine on extracellular gamma-aminobutyric acid levels in the striatum. Biochem Pharmacol 63(1):57–64. https://doi.org/10.1016/S0006-2952(00)00244-6

    Article  CAS  PubMed  Google Scholar 

  • Patek DR, Hellerman L (1974) Mitochondrial monoamine-oxidase—mechanism of inhibition by phenylhydrazine and by aralkylhydrazines—role of enzymatic oxidation. J Biol Chem 249(8):2373–2380

    CAS  PubMed  Google Scholar 

  • Pavlin M, Mavri J, Repic M, Vianello R (2013) Quantum-chemical approach to determining the high potency of clorgyline as an irreversible acetylenic monoamine oxidase inhibitor. J Neural Transm 120(6):875–882. https://doi.org/10.1007/s00702-013-1016-y

    Article  CAS  PubMed  Google Scholar 

  • Pearce LB, Roth JA (1985) Human-brain monoamine-oxidase type-B—mechanism of deamination as probed by steady-state methods. Biochemistry 24(8):1821–1826

    CAS  PubMed  Google Scholar 

  • Peng L, Zhang G, Zhang D, Wang Y, Zhu D (2010) A direct continuous fluorometric turn-on assay for monoamine oxidase B and its inhibitor-screening based on the abnormal fluorescent behavior of silole. Analyst 135(7):1779–1784

    CAS  PubMed  Google Scholar 

  • Petzer A, Harvey BH, Wegener G, Petzer JP (2012) Azure B, a metabolite of methylene blue, is a high-potency, reversible inhibitor of monoamine oxidase. Toxicol App Pharmacol 258(3):403–409

    CAS  Google Scholar 

  • Pisani L, Catto M, Leonetti F, Nicolotti O, Stefanachi A, Campagna F, Carotti A (2011) Targeting monoamine oxidases with multipotent ligands: an emerging strategy in the search of new drugs against neurodegenerative diseases. Curr Med Chem 18(30):4568–4587

    CAS  PubMed  Google Scholar 

  • Pisani L et al (2013) Fine molecular tuning at position 4 of 2H-chromen-2-one derivatives in the search of potent and selective monoamine oxidase B inhibitors. Eur J Med Chem 70:723–739. https://doi.org/10.1016/j.ejmech.2013.09.034

    Article  CAS  PubMed  Google Scholar 

  • Prusevich P et al (2014) A selective phenelzine analogue inhibitor of histone demethylase LSD1. ACS Chem Biol 9(6):1284–1293. https://doi.org/10.1021/cb500018s

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Qin XZ, Williams F (1987) ESR studies on the radical cation mechanism of the ring opening of cyclopropylamines. J Am Chem Soc 109(2):595–597. https://doi.org/10.1021/ja00236a055

    Article  CAS  Google Scholar 

  • Ramadan ZB, Wrang ML, Tipton KF (2007) Species differences in the selective inhibition of monoamine oxidase (1-methyl-2-phenylethyl)hydrazine and its potentiation by cyanide. Neurochem Res 32(10):1783–1790. https://doi.org/10.1007/s11064-007-9309-x

    Article  CAS  PubMed  Google Scholar 

  • Ramsay RR (1991) Kinetic mechanism of monoamine oxidase-A. Biochemistry 30(18):4624–4629

    CAS  PubMed  Google Scholar 

  • Ramsay RR (1998)  Substrate regulation of monoamine oxidases. J Neural Transm-Suppl 52:139-147

    CAS  PubMed  Google Scholar 

  • Ramsay RR, Hunter DJB (2002) Inhibitors alter the spectrum and redox properties of monoamine oxidase A. BBA Proteins Proteom 1601(2):178–184

    CAS  Google Scholar 

  • Ramsay RR, Tipton KF (2017) Assessment of enzyme inhibition: a review with examples from the development of monoamine oxidase and cholinesterase inhibitory drugs. Molecules (Basel, Switzerland). https://doi.org/10.3390/molecules22071192

    Article  Google Scholar 

  • Ramsay RR, Koerber SC, Singer TP (1987) Stopped-flow studies on the mechanism of oxidation of N-methyl-4-phenyltetrahydropyridine by bovine liver monoamine oxidase-B. Biochemistry 26(11):3045–3050

    CAS  PubMed  Google Scholar 

  • Ramsay RR, Sablin SO, Singer TP (1995) Redox properties of the flavin cofactor of monoamine oxidases A and B and their relationship to the kinetic mechanism. Prog Brain Res 106:33–39

    CAS  PubMed  Google Scholar 

  • Ramsay RR, Upadhyay AK, Li M, Edmondson DE (eds) (2005) Optical and EPR spectroscopic studies on the anionic flavin radical in MAO B and its Y435 mutant forms. Flavins and flavoproteins 2005. ArchiTect Inc., Tokyo

    Google Scholar 

  • Ramsay RR, Dunford C, Gillman PK (2007) Methylene blue and serotonin toxicity: inhibition of monoamine oxidase A (MAO A) confirms a theoretical prediction. Br J Pharmacol 152(6):946–951

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ramsay RR, Olivieri A, Holt A (2011) An improved approach to steady-state analysis of monoamine oxidases. J Neural Transm 118(7):1003–1019

    CAS  PubMed  Google Scholar 

  • Rebrin I, Geha RM, Chen K, Shih JC (2001) Effects of carboxyl-terminal truncations on the activity and solubility of human monoamine oxidase B. J Biol Chem 276(31):29499–29506

    CAS  PubMed  Google Scholar 

  • Reck F, Zhou F, Girardot M, Kern G, Eyermann CJ, Hales NJ, Ramsay RR, Gravestock MB (2005) Identification of 4-substituted 1,2,3-triazoles as novel oxazolidinone antibacterial agents with reduced activity against monoamine oxidase A. J Med Chem 48(2):499–506

    CAS  PubMed  Google Scholar 

  • Reynolds GP, Rausch WD, Riederer P (1980) Effects of tranylcypromine stereoisomers on monamine oxidation in man. Br J Clin Pharmacol 9(5):521–523

    CAS  PubMed  PubMed Central  Google Scholar 

  • Riederer P, Jellinger K (1983) Neurochemical insights into monoamine oxidase inhibitors, with special reference to deprenyl (selegiline). Acta Neurol Scand Suppl 95:43–55

    CAS  PubMed  Google Scholar 

  • Rigby SEJ, Hynson RMG, Ramsay RR, Munro AW, Scrutton NS (2005) A stable tyrosyl radical in monoamine oxidase A. J Biol Chem 280(6):4627–4631

    CAS  PubMed  Google Scholar 

  • Rusjan PM, Wilson AA, Miler L, Fan I, Mizrahi R, Houle S, Vasdev N, Meyer JH (2014) Kinetic modeling of the monoamine oxidase B radioligand [(1)(1)C]SL25.1188 in human brain with high-resolution positron emission tomography. J Cereb Blood Flow Metab 34(5):883–889. https://doi.org/10.1038/jcbfm.2014.34

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sablin SO, Ramsay RR (2001) Substrates but not inhibitors alter the redox potentials of monoamine oxidases. Antioxid Redox Signal 3(5):723–729

    CAS  PubMed  Google Scholar 

  • Salsali M, Holt A, Baker GB (2004) Inhibitory effects of the monoamine oxidase inhibitor tranylcypromine on the cytochrome P450 enzymes CYP2C19, CYP2C9, and CYP2D6. Cell Mol Neurobiol 24(1):63–76

    CAS  PubMed  Google Scholar 

  • Santillo MF (2014) Inhibition of monoamine oxidase (MAO) by alpha-ethylphenethylamine and N,alpha-diethylphenethylamine, two compounds related to dietary supplements. Food Chem Toxicol 74:265–269. https://doi.org/10.1016/j.fct.2014.10.009

    Article  CAS  PubMed  Google Scholar 

  • Sara W, Valette H, Peyronneau M-A, Bramoullé Y, Coulon C, Curet O, George P, Dollé F, Bottlaender M (2010) [11C]SL25.1188, a new reversible radioligand to study the monoamine oxidase type B with PET: preclinical characterisation in nonhuman primate. Synapse 64(1):61–69. https://doi.org/10.1002/syn.20703

    Article  CAS  Google Scholar 

  • Schmidt DMZ, McCafferty DG (2007) trans-2-Phenylcyclopropylamine is a mechanism-based inactivator of the histone demethylase LSD1. Biochemistry 46(14):4408–4416

    CAS  PubMed  Google Scholar 

  • Shepard EM, Heggem H, Juda GA, Dooley DM (2003) Inhibition of six copper-containing amine oxidases by the antidepressant drug tranylcypromine. BBA Proteins Proteom 1647(1–2):252–259

    CAS  Google Scholar 

  • Silverman RB (1983) Mechanism of inactivation of monoamine-oxidase by trans-2-phenylcyclopropylamine and the structure of the enzyme-inactivator adduct. J Biol Chem 258(24):14766–14769

    CAS  PubMed  Google Scholar 

  • Silverman RB (1995a) Mechanism-based enzyme inactivators. Enzyme Kinet Mech 249:240–283

    CAS  Google Scholar 

  • Silverman RB (1995b) Mechanism-based enzyme inactivators. In: Enzyme kinetics and mechanism, Pt D. Methods Enzymol 249:240–283

  • Silverman RB (1995c) Radical ideas about monoamine-oxidase. Acc Chem Res 28(8):335–342. https://doi.org/10.1021/ar00056a003

    Article  CAS  Google Scholar 

  • Silverman RB, Hiebert CK (1988) Inactivation of monoamine oxidase-A by the monoamine oxidase-B inactivators 1-phenylcyclopropylamine, 1-benzylcyclopropylamine, and N-cyclopropyl-alpha-methylbenzylamine. Biochemistry 27(22):8448–8453

    CAS  PubMed  Google Scholar 

  • Silverman RB, Hoffman SJ (1981) N-(1-Methyl)cyclopropylbenzylamine—a novel inactivator of mitochondrial monoamine-oxidase. Biochem Biophys Res Commun 101(4):1396–1401

    CAS  PubMed  Google Scholar 

  • Silverman RB, Yamasaki RB (1984) Mechanism-based inactivation of mitochondrial monoamine-oxidase by N-(1-methylcyclopropyl)benzylamine. Biochemistry 23(6):1322–1332. https://doi.org/10.1021/bi00301a046

    Article  CAS  PubMed  Google Scholar 

  • Silverman RB, Zieske PA (1985) Mechanism of inactivation of monoamine-oxidase by 1-phenylcyclopropylamine. Biochemistry 24(9):2128–2138

    CAS  PubMed  Google Scholar 

  • Silverman RB, Zieske PA (1986) Identification of the amino-acid bound to the labile adduct formed during inactivation of monoamine-oxidase by 1-phenylcyclopropylamine. Biochem Biophys Res Commun 135(1):154–159

    CAS  PubMed  Google Scholar 

  • Sliwoski G, Kothiwale S, Meiler J, Lowe EW Jr (2014) Computational methods in drug discovery. Pharmacol Rev 66(1):334–395. https://doi.org/10.1124/pr.112.007336

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Son SY, Ma A, Kondou Y, Yoshimura M, Yamashita E, Tsukihara T (2008) Structure of human monoamine oxidase A at 2.2-angstrom resolution: The control of opening the entry for substrates/inhibitors. PNAS USA 105(15):5739–5744

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sterling J et al (2002) Novel dual inhibitors of AChE and MAO derived from hydroxy aminoindan and phenethylamine as potential treatment for Alzheimer’s disease. J Med Chem 45(24):5260–5279. https://doi.org/10.1021/jm020120c

    Article  CAS  PubMed  Google Scholar 

  • Swett LR, Martin WB, Taylor JD, Everett GM, Wykes AA, Gladish YC (1963) Structure-activity relations in the pargyline series. Ann N Y Acad Sci 107:891–898

    CAS  PubMed  Google Scholar 

  • Szewczuk LM, Culhane JC, Yang M, Majumdar A, Yu H, Cole PA (2007) Mechanistic analysis of a suicide inactivator of histone demethylase LSD1. Biochemistry 46(23):6892–6902

    CAS  PubMed  Google Scholar 

  • Talele TT (2016) The “cyclopropyl fragment” is a versatile player that frequently appears in preclinical/clinical drug molecules. J Med Chem 59(19):8712–8756. https://doi.org/10.1021/acs.jmedchem.6b00472

    Article  CAS  PubMed  Google Scholar 

  • Tan AK, Ramsay RR (1993) Substrate-specific enhancement of the oxidative half-reaction of monoamine-oxidase. Biochemistry 32(9):2137–2143

    CAS  PubMed  Google Scholar 

  • Taylor JD, Wykes AA, Gladish YC, Martin WB (1960) New inhibitor of monoamine oxidase. Nature 187:941–942. https://doi.org/10.1038/187941a0

    Article  CAS  PubMed  Google Scholar 

  • Tipton KF (1971) Reaction of monoamine oxidase with phenethylhydrazine. Biochem J 121(3):P33

    Google Scholar 

  • Tipton KF, Spires IPC (1971) Kinetics of phenethylhydrazine oxidation by monoamine oxidase. Biochem J 125(2):521–524. https://doi.org/10.1042/bj1250521

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tipton KF, Davey G, Motherway M (2006) Monoamine oxidase assays. In: Current protocols in toxicology 30:4.21:4.21.1–4.21.42

  • Tsugeno Y, Ito A (1997) A key amino acid responsible for substrate selectivity of monoamine oxidase A and B. J Biol Chem 272(22):14033–14036. https://doi.org/10.1074/jbc.272.22.14033

    Article  CAS  PubMed  Google Scholar 

  • Tzvetkov NT, Stammler HG, Neumann B, Hristova S, Antonov L, Gastreich M (2017) Crystal structures, binding interactions, and ADME evaluation of brain penetrant N-substituted indazole-5-carboxamides as subnanomolar, selective monoamine oxidase B and dual MAO-A/B inhibitors. Eur J Med Chem 127:470–492. https://doi.org/10.1016/j.ejmech.2017.01.011

    Article  CAS  PubMed  Google Scholar 

  • Umhau S, Pollegioni L, Molla G, Diederichs K, Welte W, Pilone M, Ghisla S (2000) The X-ray structure of d-amino acid oxidase at very high resolution identifies the chemical mechanism of flavin-dependent substrate dehydrogenation. PNAS USA 97(23):12463–12468. https://doi.org/10.1073/pnas.97.23.12463

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Unzeta M, Esteban G, Bolea I, Fogel WA, Ramsay RR, Youdim MBH, Tipton KF, Marco-Contelles J (2016) Multi-target directed donepezil-like ligands for Alzheimer’s disease. Front Neurosci. https://doi.org/10.3389/fnins.2016.00205

    Article  PubMed  PubMed Central  Google Scholar 

  • Upadhyay AK, Borbat PP, Wang J, Freed JH, Edmondson DE (2008) Determination of the oligomeric states of human and rat monoamine oxidases in the outer mitochondrial membrane and octyl beta-d-glucopyranoside micelles using pulsed dipolar electron spin resonance spectroscopy. Biochemistry 47(6):1554–1566

    CAS  PubMed  Google Scholar 

  • Valley MP et al (2006) A bioluminescent assay for monoamine oxidase activity. Anal Biochem 359(2):238–246. https://doi.org/10.1016/j.ab.2006.09.035

    Article  CAS  PubMed  Google Scholar 

  • Vazquez ML, Silverman RB (1985) Revised mechanism for inactivation of mitochondrial monoamine-oxidase by N-cyclopropylbenzylamine. Biochemistry 24(23):6538–6543

    CAS  PubMed  Google Scholar 

  • Veselovsky AV, Ivanov AS, Medvedev AE (2004) Computer modelling and visualization of active site of monoamine oxidases. Neurotoxicology 25(1–2):37–46

    CAS  PubMed  Google Scholar 

  • Vianello R, Repic M, Mavri J (2012) How are biogenic amines metabolized by monoamine oxidases? Eur J Org Chem 36:7057–7065

    Google Scholar 

  • Vianello P et al (2014) Synthesis, biological activity and mechanistic insights of 1-substituted cyclopropylamine derivatives: a novel class of irreversible inhibitors of histone demethylase KDM1A. Eur J Med Chem 86:352–363. https://doi.org/10.1016/j.ejmech.2014.08.068

    Article  CAS  PubMed  Google Scholar 

  • Vianello R, Domene C, Mavri J (2016) The use of multiscale molecular simulations in understanding a relationship between the structure and function of biological systems of the brain: the application to monoamine oxidase enzymes. Front Neurosci. https://doi.org/10.3389/fnins.2016.00327

    Article  PubMed  PubMed Central  Google Scholar 

  • Vintem APB, Price NT, Silverman RB, Ramsay RR (2005) Mutation of surface cysteine 374 to alanine in monoamine oxidase A alters substrate turnover and inactivation by cyclopropylamines. Bioorg Med Chem 13(10):3487–3495

    CAS  PubMed  Google Scholar 

  • Walker MC, Edmondson DE (1994) Structure-activity-relationships in the oxidation of benzylamine analogs by bovine liver mitochondrial monoamine-oxidase-B. Biochemistry 33(23):7088–7098

    CAS  PubMed  Google Scholar 

  • Wang J, Edmondson DE (2011) H-2 kinetic isotope effects and pH dependence of catalysis as mechanistic probes of rat monoamine oxidase A: comparisons with the human enzyme. Biochemistry 50(35):7710–7717. https://doi.org/10.1021/bi200951z

    Article  CAS  PubMed  Google Scholar 

  • Weinreb O, Amit T, Bar-Am O, Youdim MBH (2010) Rasagiline: a novel anti-Parkinsonian monoamine oxidase-B inhibitor with neuroprotective activity. Prog Neurobiol 92(3):330–344

    CAS  PubMed  Google Scholar 

  • Weinreb O, Amit T, Riederer P, Youdim MBH, Mandel SA (2011) Neuroprotective profile of the multitarget drug rasagiline in Parkinson’s disease. In: Youdim MBH (ed) Monoamine oxidases and their inhibitors. Int Rev Neurobiol 100:127–149

  • Werther T, Wahlefeld S, Salewski J, Kuhlmann U, Zebger I, Hildebrandt P, Dobbek H (2017) Redox-dependent substrate-cofactor interactions in the Michaelis-complex of a flavin-dependent oxidoreductase. Nat Commun 8:16084. https://doi.org/10.1038/ncomms16084

    Article  CAS  PubMed Central  Google Scholar 

  • Weyler W (1994) Functional expression of C-terminally truncated human monoamine-oxidase type-a in Saccharomyces cerevisiae. J Neural Transm Suppl 41:3–15

    CAS  PubMed  Google Scholar 

  • Williams CH, Lawson J (1974) Monoamine oxidase. II. Time-dependent inhibition by propargylamines. Biochem Pharmacol 23(3):629–636

    CAS  PubMed  Google Scholar 

  • Wu HF, Chen K, Shih JC (1993) Site-directed mutagenesis of monoamine oxidase-A and oxidase-B—role of cysteines. Mol Pharmacol 43(6):888–893

    CAS  PubMed  Google Scholar 

  • Wu XF, Li LH, Shi W, Gong QY, Li XH, Ma HM (2016) Sensitive and selective ratiometric fluorescence probes for detection of intracellular endogenous monoamine oxidase A. Anal Chem 88(2):1440–1446. https://doi.org/10.1021/acs.analchem.5b04303

    Article  CAS  PubMed  Google Scholar 

  • Xie SS, Wang XB, Jiang N, Yu WY, Wang KDG, Lan JS, Li ZR, Kong LY (2015) Multi-target tacrine-coumarin hybrids: cholinesterase and monoamine oxidase B inhibition properties against Alzheimer’s disease. Eur J Med Chem 95:153–165. https://doi.org/10.1016/j.ejmech.2015.03.040

    Article  CAS  PubMed  Google Scholar 

  • Yang HY, Neff NH (1974) The monoamine oxidases of brain: selective inhibition with drugs and the consequences for the metabolism of the biogenic amines. J Pharmacol Exp Ther 189(3):733–740

    CAS  PubMed  Google Scholar 

  • Youdim MBH, Tipton KF (2002) Rat striatal monoamine oxidase-B inhibition by l-deprenyl and rasagiline: its relationship to 2-phenylethylamine-induced stereotypy and Parkinson’s disease. Parkinsonism Relat Disord 8(4):247–253. https://doi.org/10.1016/s1353-8020(01)00011-6

    Article  CAS  PubMed  Google Scholar 

  • Youdim MB, Collins GG, Sandler M (1971) Monoamine oxidase: multiple forms and selective inhibitors. Biochem J 121:32P–34P

    Google Scholar 

  • Youdim MBH, Wadia A, Tatton W, Weinstock M (2001) The anti-Parkinson drug rasagiline and its cholinesterase inhibitor derivatives exert neuroprotection unrelated to MAO inhibition in cell culture and in vivo. In: Slikker W, Trembly B (eds) Neuroprotective agents. Ann N Y Acad Sci, vol 939, pp 450–458

  • Youdim MBH, Edmondson D, Tipton KF (2006) The therapeutic potential of monoamine oxidase inhibitors. Nat Rev Neurosci 7(4):295–309

    CAS  PubMed  Google Scholar 

  • Youngster SK, McKeown KA, Jin YZ, Ramsay RR, Heikkila RE, Singer TP (1989) Oxidation of analogs of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine by monoamine oxidase-A and oxidase-B and the inhibition of monoamine oxidases by the oxidation products. J Neurochem 53(6):1837–1842

    CAS  PubMed  Google Scholar 

  • Yu PH (1994) Pharmacological and clinical implications of MAO-B inhibitors. Gen Pharmacol 25(8):1527–1539

    CAS  PubMed  Google Scholar 

  • Yu PH, Tipton KF (1989) Deuterium-isotope effect of phenelzine on the inhibition of rat-liver mitochondrial monoamine-oxidase activity. Biochem Pharmacol 38(23):4245–4251

    CAS  PubMed  Google Scholar 

  • Yu PH, Bailey BA, Durden DA, Boulton AA (1986) Stereospecific deuterium substitution at the alpha-carbon position of dopamine and its effect on oxidative deamination catalyzed by MAOA and MAOB from different tissues. Biochem Pharmacol 35(6):1027–1036

    CAS  PubMed  Google Scholar 

  • Zeller EA, Barsky J (1952) In vivo inhibition of liver and brain monoamine oxidase by 1-isonicotinyl-2-isopropyl hydrazine. Proc Soc Exper Bio Med 81(2):459–461

    CAS  Google Scholar 

  • Zeller EA, Sarkar S (1962) Amine oxidases. XIX. Inhibition of monoamine oxidase by phenylcyclopropylamines and iproniazid. J Biol Chem 237:2333–2336

    CAS  PubMed  Google Scholar 

  • Zenn RK, Abad E, Kastner J (2015) Influence of the environment on the oxidative deamination of p-substituted benzylamines in monoamine oxidase. J Phys Chem B 119(9):3678–3686. https://doi.org/10.1021/jp512470a

    Article  CAS  PubMed  Google Scholar 

  • Zhong BY, Silverman RB (1997) Identification of the active site cysteine in bovine liver monoamine oxidase B. J Am Chem Soc 119(28):6690–6691

    CAS  Google Scholar 

Download references

Acknowledgements

The authors thank COST Action CM1103.

Author information

Author notes

  1. Alen Albreht

    Present address: Department of Analytical, Environmental and Forensic Sciences, Faculty of Life Sciences and Medicine, King’s College London, Franklin-Wilkins Building, London, SE1 8WA, UK

Authors and Affiliations

  1. Biomedical Sciences Research Complex, University of St Andrews, North Haugh, St Andrews, KY16 8QP, UK

    Rona R. Ramsay

  2. Department of Food Chemistry, National Institute of Chemistry, Hajdrihova 19, 1000, Ljubljana, Slovenia

    Alen Albreht

Authors
  1. Rona R. Ramsay
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alen Albreht
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rona R. Ramsay.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ramsay, R.R., Albreht, A. Kinetics, mechanism, and inhibition of monoamine oxidase. J Neural Transm 125, 1659–1683 (2018). https://doi.org/10.1007/s00702-018-1861-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00702-018-1861-9

Keywords

Search

Navigation