Overview of the present state of MAO inhibitors

  • Margherita Strolin Benedetti
  • P. Dostert
Part of the Journal of Neural Transmission book series (NEURAL SUPPL, volume 23)


In this paper an overview of the present state of monoamine oxidase inhibitors (MAOIs) is presented. The irreversible inhibitors are firstly considered. They have been divided into four chemical types: substituted hydrazine, cyclopropylamine, propargylamine and allylamine derivatives. Moreover, a tetrahydropyridine derivative (MPTP), recently described as an irreversible inhibitor of MAO-B, has been included among the irreversible MAOIs.

The reversible inhibitors such as tetrahydro-β-carbolines and salsolinol, phenylalkylamines:amphetamine, amiflamine and 2,3-dicholoro-α-methyl-benzylamine.

Among the short acting or reversible inhibitors the 4-(2-benzofuranyl) piperidine series and the morpholinoethylamino derivatives are discussed.

Finally the oxazolidinone series is presented separately, as in this series reversible or irreversible inhibitors of the A or B form of MAO have been obtained.


Monoamine Oxidase Reversible Inhibitor Amine Oxidase Irreversible Inhibitor Oxidative Deamination 


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  1. Alston TA (1981) Suicide substrates for mitochondrial enzymes. Pharmac Ther 12: 1–41CrossRefGoogle Scholar
  2. Ask AL, Fagervall I, Florvall L, Ross SB, Ytterborn S (1986) Selective inhibition of monoamine oxidase by p-aminosubstituted phenylalkylamines in catecholaminergic neurones. Neuropharmacology 25: 33–40PubMedCrossRefGoogle Scholar
  3. Belleau B, Moran J (1963) Deuterium isotope effects in relation to the chemical mechanism of monoamine oxidase. Ann NY Acad Sci 107: 822–839PubMedCrossRefGoogle Scholar
  4. Birkmayer W, Riederer P, Linauer W, Knoll J (1984) L-deprenyl plus L-phenylalanine in the treatment of depression. J Neural Transm 59: 81–87PubMedCrossRefGoogle Scholar
  5. Biziere K, Bougault I, Kan JP, Mouget-Goniot C, Mons G, Worms P (1985) Effect of two amino-pyridazine derivatives on both forms of monoamine oxidase in rat brain. Br J Pharmacol 86 [Suppl]: 417 PGoogle Scholar
  6. Boucher T, Strolin Benedetti M, Dostert P, Tipton KF (1987) II nd amine oxidase meeting, Uppsala, 2–4 August 1986. Acta Pharmacol Toxicol (in press)Google Scholar
  7. Buckman TD, Sutphin MS, Eiduson S (1984) Proteases as probes of mitochondrial monoamine oxidase topography in situ. Mol Pharmacol 25: 165–170PubMedGoogle Scholar
  8. Calzetti S, Baratti M (1985) A double-blind controlled study of the short-term effect of deprenyl (selegiline) combined with bromocriptine in early Parkinson’s disease. 8th international symposium of Parkinson’s disease, 9–12 June 1985, New York (abstract book, p 122)Google Scholar
  9. Cesura AM, Kettler R, Da Prada M (1985) Binding of 3H-Ro 16–6491 in human brain and platelets: characterization of MAO-B. J Neurochem 44 [Suppl]: S179Google Scholar
  10. Chiba K, Trevor A, Castagnoli N Jr (1984) Metabolism of the neurotoxic tertiary amine, MPTP, by brain monoamine oxidase. Biochem Biophys Res Commun 120: 574–578PubMedCrossRefGoogle Scholar
  11. Ciba-Geigy (1986) Sercloremine hydrochloride. Drugs of the Future 11:126–128Google Scholar
  12. Collins MA, Neafsey EJ (1985) ß-carboline analogues of N-methyl-4-phe-nyl-1,2, 5, 6-tetrahydropyridine (MPTP): endogenous factors underlying idiopathic Parkinsonism? Neurosci Lett 55: 179–184Google Scholar
  13. Da Prada M, Kettler R, Keller HH, Bonetti EP, Imhof R (1986) Ro 16–6491: a new reversible and highly selective MAO-B inhibitor protects mice from the dopaminergic neurotoxicity of MPTP. In: Yahr MD, Berg-mann KJ (eds) Adv neurol, vol 45. Raven Press, New York, pp l75–178Google Scholar
  14. Da Prada M, Kettler R, Keller HH, Kyburz E, Burkhard WP (1987) IInd amine oxidase meeting, Uppsala, 2–4 August 1986. Acta Pharmacol Toxicol (in press)Google Scholar
  15. Denney RM, Fritz RR, Patel NT, Widen SG, Abell CW (1983) Use of a monoclonal antibody for comparative studies of monoamine oxidase B in mitochondrial extracts of human brain and peripheral tissues. Mol Pharmacol 24: 60–68PubMedGoogle Scholar
  16. Dostert P, Strolin Benedetti M (1986) Nouveaux inhibiteurs de la monoamine oxydase. Actual Chim Ther 13eme serie, Lavoisier, Paris, pp 269– 287Google Scholar
  17. Elsworth JD, Sandler M, Lees AJ, Ward C, Stern GM (1982) The contribution of amphetamine metabolites of (–)-deprenyl to its antiparkinsonian properties. J Neural Transm 54: 105–110PubMedCrossRefGoogle Scholar
  18. Fowler CJ, Ross SB (1984) Selective inhibitors of monoamine oxidase A and B: biochemical, pharmacological, and clinical properties. Med Res Rev 4: 323–358PubMedCrossRefGoogle Scholar
  19. Fozard JR, Zreika M, Robin M, Palfreyman MG (1985) The functional consequences of inhibition of monoamine oxidase type B: comparison of the pharmacological properties of L-deprenyl and MDL 72145. Naunyn Schmiedeberg’s Arch Pharmacol 331: 186–193CrossRefGoogle Scholar
  20. Fozard JR, Palfreyman MG, Robin M, Zreika M (1986) Selective inhibition of monoamine oxidase type B by MDL 72145 increases the central effects of L-Dopa without modifying its cardiovascular effects. Br J Pharmacol 87: 257–264PubMedGoogle Scholar
  21. Fuller RW, Hemrick SK (1978) Steric influence on inhibition of monoamine oxidase forms by 2,3-dichloro-a-methylbenzylamine. Res Commun Chem Pathol Pharmacol 20: 199–202PubMedGoogle Scholar
  22. Fuller RW, Hemrick-Luecke SK (1985) Inhibition of types A and B monoamine oxidase by l-methyl-4-phenyl-l, 2,3, 6-tetrahydropyridine. J Pharmacol Exp Ther 232: 696–701PubMedGoogle Scholar
  23. Kalir A, Sabbagh A, Youdim MBH (1981) Selective acetylenic “suicide” and reversible inhibitors of monoamine oxidase types A and B. Br J Pharmac 73: 55–64Google Scholar
  24. Kan JP, Strolin Benedetti M (1981) Characteristics of the inhibition of rat brain monoamine oxidase in vitro by MD 780515. J Neurochem 36: 1561–1571PubMedCrossRefGoogle Scholar
  25. Keller HH, Kettler R, Keller G, Da Prada M (1986) Short-acting novel MAO-inhibitors: in vitro evidence for reversibility of MAO inhibition. Naunyn Schmiedeberg’s Arch Pharmacol 332 [Suppl]: R74Google Scholar
  26. Kenney WC, Nagy J, Salach JI, Singer TP (1979) Structure of the covalent phenylhydrazine adduct of monoamine oxidase. In: Singer TP, Von Korff RW, Murphy DL (eds) Monoamine oxidase: structure, function and altered functions. Academic Press, New York, pp25–37Google Scholar
  27. Knoll J, Ecsery Z, Magyar K, Satory E (1978) Novel (–)deprenyl-derived selective inhibitors of B-type monoamine oxidase. The relation of structure to their action. Biochem Pharmacol 27: 1739–1747PubMedCrossRefGoogle Scholar
  28. Lesage A, Strolin Benedetti M, Rumigny JF (1984) High affinity binding site for (+)amphetamine in rat hypothalamus: fact or artefact? Neurochem Int 6: 283–286PubMedCrossRefGoogle Scholar
  29. Lesage A, Strolin Benedetti M, Rumigny JF (1985) Evidence that (+)[3H] amphetamine binds to acceptor sites wich are not MAO-A. Biochem Pharmacol 34: 3000–3002PubMedCrossRefGoogle Scholar
  30. Lewin R (1985) Clinical trial for Parkinson’s disease? Science 230: 527–528PubMedCrossRefGoogle Scholar
  31. Magyar K, Ecseri Z, Bernath G, Satory E, Knoll J (1979) Structure-activity relationship of selective inhibitors of MAO-B. In: Magyar K (ed) Monoamine oxidases and their selective inhibition. Pergamon Press Advances in pharmacological research and practice, vol 4, pp 11–21Google Scholar
  32. McDonald IA, Palfreyman MG, Zreika M, Bey P, (1986) (Z)-2-(2,4-dichloro-phenoxy)methyl-3-fluoroallylamine (MDL 72638): a clorgyline analogue with surprising selectivity for monoamine oxidase type B. Biochem Pharmacol 35: 349–351PubMedCrossRefGoogle Scholar
  33. Meller E, Friedman E, Schweitzer JW, Friedhoff AJ (1977) Tetrahydro-ß-car-bolines: specific inhibitors of type A monoamine oxidase in rat brain. J Neurochem 28: 995–1000PubMedCrossRefGoogle Scholar
  34. Meyerson LR, McMurtrey KD, Davis VE (1976) Neuroamine-derived alkaloids: substrate-preferred inhibitors of rat brain monoamine oxidase in vitro. Biochem Pharmacol 25: 1013–1020PubMedCrossRefGoogle Scholar
  35. Nelson DL, Herbet A, Petillot Y, Pichat L, Glowinski J, Hamon M (1979) (3H) Harmaline as a specific ligand of MAO-A-I. Properties of the active site of MAO-A from rat and bovine brains. J Neurochem 32:1817–1827PubMedCrossRefGoogle Scholar
  36. Palfreyman MG, McDonald IA, Bey P, Danzin C, Zreika M, Lyles GA, Fozard JR (1986) The rational design of suicide substrates of amine oxidases. Biochem Soc Trans 14: 410–413PubMedGoogle Scholar
  37. Paul SM, Hulihan-Giblin B, Skolnick P (1982) (+)-Amphetamine binding to rat hypothalamus: relation to anorectic potency of phenylethylamines. Science 218: 487–490Google Scholar
  38. Pearce LB, Roth JA (1984) Monoamine oxidase: separation of the type A and B activities. Biochem Pharmacol 33: 1809–1811PubMedCrossRefGoogle Scholar
  39. Porsolt RD, Pawelec C, Roux S, Jalfre M (1984) Discrimination of the amphetamine cue. Effects of A, B and mixed type inhibitors of monoamine oxidase. Neuropharmacology 23: 569–573PubMedCrossRefGoogle Scholar
  40. Rando RR, Eigner A (1977) The pseudoirreversible inhibition of monoamine oxidase by allylamine. Mol Pharmacol 13: 1005–1013PubMedGoogle Scholar
  41. Richard C, Guichard JP, Strolin Benedetti M, Dostert P (1987) Effect of MAO inhibitors on in vivo lipid peroxidation. IInd amine oxidase meeting, Uppsala, 2–4 August 1986. Acta Pharmacol Toxicol (in press)Google Scholar
  42. Riederer P, Jellinger K, Seemann D (1984) Monoamine oxidase and parkinsonism. In: Tipton KF, Dostert P, Strolin Benedetti M (eds) Monoamine oxidase and disease. Prospects for therapy with reversible inhibitors. Academic Press, London, pp 403–415Google Scholar
  43. Riley TN, Brier CG (1972) Absolute configuration of (+)- and (-)-trans-2-phenylcyclopropylamine hydrochloride. J Med Chem 15: 1187– 1188Google Scholar
  44. Russel SM, Davey J, Mayer RJ (1979) The vectorial orientation of human monoamine oxidase in the mitochondrial outer membrane. BiochemJ 181: 7–14Google Scholar
  45. Silverman RB (1983) Mechanism of inactivation of monoamine oxidase by trans-2-phenylcyclopropylamine and the structure of the enzyme-in-activator adduct. J Biol Chem 258: 14766–14769PubMedGoogle Scholar
  46. Silverman RB, Hoffman SJ (1980) Mechanism of inactivation of mitochondrial monoamine oxidase by N-cyclopropyl-N-arylalkyl amines. J Am Chem Soc 102: 884–886CrossRefGoogle Scholar
  47. 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: 154– 159Google Scholar
  48. Singer TP (1979) Active site-directed, irreversible inhibitors of monoamine oxidase. In: Singer TP, Von Korff RW, Murphy DL (eds) Monoamine oxidase: structure, function and altered functions. Academic Press, New York, pp 7–24Google Scholar
  49. Singer TP, Salach JI (1981) Interaction of suicide inhibitors with the active site of monoamine oxidase. In: Youdim MBH, Paykel ES (eds) Monoamine oxidase inhibitors–the state of the art. J Wiley, New York, pp 17–29Google Scholar
  50. Strolin Benedetti M (1984) Some pharmacological and clinical aspects of reversible MAO inhibitors. In: Paton W, Mitchell J, Turner P (eds) Proceedings vol 2, IUPHAR 9th int congress of pharmacology, London, 1984. Macmillan, Basingstoke, pp 219–230Google Scholar
  51. Strolin Benedetti M, Dostert P (1985) Stereochemical aspects of MAO interactions: reversible and selective inhibitors of monoamine oxidase. TIPS 6: 246–251Google Scholar
  52. Strolin Benedetti M, Dow J, Boucher T, Dostert P (1983) Metabolism of the monoamine oxidase-B inhibitor, MD 780236 and its enantiomers by the A and B forms of the enzyme in the rat. J Pharm Pharmacol 35: 837–840PubMedCrossRefGoogle Scholar
  53. Waldmeier PC, Felner AE, Tipton KF, (1983 a) The monoamine oxidase inhibiting properties of CGP11305 A. Eur J Pharmacol 94: 73–83PubMedCrossRefGoogle Scholar
  54. Waldmeier PC, Feldtrauer JJ, Stoecklin K, Paul E, (1983 b) Reversibility of the interaction of CGP11305 A with MAO A in vivo. Eur J Pharmacol 94: 101–108PubMedCrossRefGoogle Scholar
  55. Westlund KN, Denney RM, Kochersperger LM, Rose RM, Abell CW (1985) Distinct monoamine oxidase A and B populations in primate brain. Science 230: 181–183PubMedCrossRefGoogle Scholar
  56. Yu PH, Bailey BA, Durden DA, Boulton AA (1986) Stereospecific deuterium substitution at the a-carbon position of dopamine and its effect on oxidative deamination catalyzed by MAO-A and MAO-B from different tissues. Biochem Pharmacol 35: 1027–1036PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag/Wien 1987

Authors and Affiliations

  • Margherita Strolin Benedetti
    • 1
  • P. Dostert
    • 1
  1. 1.Laboratoires FournierCentre de Recherches de DaixFontaine-les-DijonFrance

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