Skip to main content
SpringerLink
Log in

Medicinal Chemistry of Present and Future MAO-B Inhibitors

  • Chapter
Inhibitors of Monoamine Oxidase B

Part of the book series: Milestones in Drug Therapy ((MDT))

Abstract

The first monoamine oxidase (MAO) inhibitor was described 26 years before the discovery of the enzyme itself. As late as the mid-1900s millions of patients still suffered from tuberculosis. Then, several groups of chemists synthesized molecules with different chemical structures in attempts to create an efficient treatment for this illness. One of these compounds, isonicotinyl hydrazide (isoniazid) was originally synthesized as a necessary intermediary but was later described as an antitu-berculotic agent. This substance was, in essence, the first MAO inhibitor, and it had been described as early as 1912, without regard to its biological activity. Among its monoalkyl derivatives the 2-isopropyl-1-isonicotinyl hydrazide (iproniazid) was the most effective in clinical practice. Its unwanted “lightening” side-effect had been the starting point for pharmacological therapy of depression 1.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 49.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 69.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Crane GE. Psychiatric side effects of iproniazid. Am J Psychiatry 1956; 112: 494–497.

    Google Scholar 

  2. Zeller AA, Barsky J. In vivo inhibition of liver and brain monoamine oxidase by l-isonicotinyl-2-isopropyl hydrazine. Proc Soc Exp Biol Med 1952; 81: 459–461.

    Google Scholar 

  3. Zeller EA, Barsky J, Fouts JR, Kirchheimer WF, van Orden LS. Influence of isonico- tinic acid hydrazide and l-isonicotinyl-2-isopropylhydrazide on bacterial and mammalian enzymes. Experientia 1952; 8: 349–350.

    Google Scholar 

  4. Youdim MBH, Finberg JMP. Monoamine oxidase inhibitors. In: Grahame-Smith DG, Cowen PE, editors. Psychopharmacology. Part 1, Preclinical Psychopharmacology. Amsterdam: Excerpta Medica, 1983: 37–51.

    Google Scholar 

  5. Murphy DL, Garrick NA, Aulakh CS, Cohen RM. New contributions from basic science to understanding the effects of monoamine oxidase inhibiting antidepressants. J Clin Psychiatry 1984; 45: 37–43.

    Google Scholar 

  6. Knoll J, Ecsery JG, Nievel J, Knoll B. Phenylisopropylmethylpropinylamine HCl (E-250), egy új hatásspektrumú psychoenergetikum. MTA V Oszt Közl 1964; 15: 231–239.

    Google Scholar 

  7. Johnston JP. Some observations upon a new inhibitor of monoamine oxidase in brain tissue. Biochem Pharmacol 1968; 17: 1285–1297.

    Google Scholar 

  8. Knoll, J, Magyar K. Some puzzling pharmacological effects of monoamine oxidase inhibitors. Adv Biochem Psychopharm 1972; 5: 393–408.

    Google Scholar 

  9. Silverman RB, Hoffman SJ, Catus WB. III. A mechanism for mitochondrial monoamine oxidase catalyzed amine oxidation. J Amer Chem Soc 1980; 102: 7126–7128.

    Google Scholar 

  10. White HL, Tansik RL. Characterization of multiple substrate binding sites of MAO. In: Singer TP, Von Korff RW, Murphy DL, editors. Monoamine oxidase: structure, function and altered functions. London: Academic Press, 1979: 129–144.

    Google Scholar 

  11. Denney RM, Fritz RR, Patel NT, Abell CW. Human liver MAO-A and MAO-B separated by immunoaffinity chromatography with MAO-B-specific monoclonal antibody. Science 1982; 215: 1400–1403.

    Google Scholar 

  12. Kochersperger LM, Waguespack A, Patterson JC, Hsieh CC, Weyler W, Salach JI, et al. Immunological uniqueness of human monoamine oxidase A and B; new evidence from studies with monoclonal antibodies to human monoamine oxidase A. J Neurosci 1985; 5: 2874–2881.

    Google Scholar 

  13. Kinemuchi H, Arai Y, Toyoshima Y, Tadano T, Kisara K. Studies on 5-fluoro-alpha- methyltryptamine and p-chloro-beta-methylphenethylamine: Determination of the MAO-A or MAO-B selective inhibition in vitro. Jap J Pharmac 1988; 46: 197–199.

    Google Scholar 

  14. Westlund KN, Denney RM, Kochersperger LM, Rose RM, Abell CW. Distinct monoamine oxidase A and B populations in primate brain. Science 1985; 230: 181–183.

    Google Scholar 

  15. Cawthon RM, Pintar JE, Haseltine FP, Breakefield XO. Differences in the structure of A and B forms of human monoamine oxidase. J Neurochem 1981; 37: 363–372.

    Google Scholar 

  16. Smith D, Filipowicz C, McCauley R. Monoamine oxidase A and monoamine oxidase B activities are catalyzed by different proteins. Biochim Biophys Acta 1985; 831: 1–7.

    Google Scholar 

  17. Bach AWJ, Lan NC, Johnson DL, Abbel CW, Bembenek ME, Kwan S-W, et al. cDNA cloning of human liver monoamine oxidase A and B: Molecular basis of differences in enzymatic properties. Proc Natl Acad Sci 1988; 85: 4934–4938.

    Google Scholar 

  18. Chuang HYK, Patek DR, Hellerman L. Mitochondrial monoamine oxidase. J Biol Chem 1974; 249: 2381–2384.

    Google Scholar 

  19. Powell JF, Hsu Y-PP, Weyler W, Chen S, Salach J, Andrikopoulos K, Mallet J and Breakefield XO. The primary structure of bovine monoamine oxidase type A. Comparison with peptide sequences of bovine monoamine oxidase type B and other flavoenzymes. Biochem J 1989; 259: 407–413.

    Google Scholar 

  20. Weyler W, Salach JI. Purification and properties of mitochondrial monoamine oxidase type A from human placenta. J Biol Chem 1985; 260: 13199–13207.

    Google Scholar 

  21. Von Korff RW. Monoamine oxidase: unanswered questions. In: Singer TP, Von Korff RW, Murphy DL, editors. Monoamine oxidase: structure, function and altered functions. New York: Academic Press, 1979: 1–6.

    Google Scholar 

  22. Kyburz E. New development in the field of MAO inhibitors. ND&P 1990; 3: 592–599.

    Google Scholar 

  23. Yu PH. Studies on the pargyline-binding site of different types of monoamine oxidase. Can J Biochem 1981; 59: 30–37.

    Google Scholar 

  24. Kearney EB, Salach JI, Walker WH, Seng RL, Kenney W, Zeszotek E, et al. The covalently-bound flavin of hepatic monoamine oxidase. I. Isolation and sequence of a flavin peptide and evidence for binding at the 8 position. Eur J Biochem 1971; 24: 321–327.

    Google Scholar 

  25. Kalir A, Sabbagh A, Youdim MBH. Selective acetylenic “suicide” and reversible inhibitors of monoamine oxidase types A and B. Br J Pharm 1981; 73: 55–64.

    Google Scholar 

  26. Naoi M, Yagi K. Effects of phospholipids on beef heart mitochondrial monoamine oxidase. Arch Biochem Biophys 1980; 205: 18–26.

    Google Scholar 

  27. Singer TP. Perspectives in MAO: past, present and future. J Neurol Transm 1987 suppl.; 23: 1–23.

    Google Scholar 

  28. Erwin VG, Hellerman L. Mitochondrial monoamine oxidase. I. Purification and characterization of the bovine kidney enzyme. J Biol Chem 1967; 242: 4230–4238.

    Google Scholar 

  29. Husain M, Edmondson DE, Singer TP. Catalytic mechanism of MAO from liver. In: Usdin E, Weiner N, Youdim MBH, editors. Function and regulation of monoamine enzymes. London: Macmillan, 1981; 477–487.

    Google Scholar 

  30. Huang RH, Faulkner R. The role of phospholipids in the multiple forms of brain monoamine oxidase. J Biol Chem 1981; 256: 9211–9215.

    Google Scholar 

  31. Blaschko H, Richter D, Schlossmann H. The oxidation of adrenaline and other amines. Biochem J 1937; 31: 2187–2196.

    Google Scholar 

  32. Pugh CEM, Quastel JH. Oxidation of aliphatic amines by brain and other tissues. Biochem J 1937; 31: 286–291.

    Google Scholar 

  33. Kohn HI. Tyramine oxidase. Biochem J 1937; 31: 1693–1704.

    Google Scholar 

  34. Alles GA, Heegaard EV. Substrate specificity of amine oxidase. J Biol Chem 1943; 147: 487–503.

    Google Scholar 

  35. Bhagvat K, Blaschko H, Richter D. Amine oxidase. Biochem J 1939; 33: 1338–1341.

    Google Scholar 

  36. Fowler CJ, Callingham BA, Mantle TJ, Tipton KF. Monoamine oxidase A and B: a useful concept? Biochem Pharmacol 1978; 27: 97–101.

    Google Scholar 

  37. Neff NH, Yang H-YT, Goridis C, Bialek D. The metabolism of indolealkylamines by type A and B monoamine oxidase of brain. Adv Biochem Psychopharmacol 1974; 11: 51–58.

    Google Scholar 

  38. Fowler CJ, Tipton KF. Concentration dependence of the oxidation of tyramine by the two forms of rat liver mitochondrial monoamine oxidase. Biochem Pharmacol 1981; 30: 3329–3332.

    Google Scholar 

  39. Strolin Benedetti M, Boucher Th, Carlsson A, Fowler CJ. Intestinal metabolism of tyramine by both forms of monoamine oxidase in the rat. Biochem Pharmacol 1983; 32: 47–52.

    Google Scholar 

  40. Schoepp DD, Azzaro AJ. Specificity of endogeneous substrates for types A and B monoamine oxidase in rat striatum. J Neurochem 1981; 36: 2025–2031.

    Google Scholar 

  41. Kinemuchi H, Wakui Y, Kamijo K. Substrate selectivity of type A and B monoamine oxidase in rat brain. J Neurochem 1980; 35: 109–115.

    Google Scholar 

  42. Parkinson D, Lyles GA, Browne BJ, Callingham BA. Some factors influencing the metabolism of benzylamine by type A and B monoamine oxidase in rat heart and liver. J Pharm Pharmacol 1980; 32: 844–850.

    Google Scholar 

  43. Guffroy C, Fowler CJ, Strolin Benedetti M. The deamination of n-pentylamine by monoamine oxidase and a semicarbazide-sensitive amine oxidase of rat heart. J Pharm Pharmacol 1983; 35: 416–420.

    Google Scholar 

  44. Tipton KF. Some properties of monoamine oxidase. Adv Biochem Psychopharmacol 1972; 5: 11–24.

    Google Scholar 

  45. George T, Kaul CL, Grewal RS, Tahilramani R. Antihypertensive and monoamine oxidase inhibitory activity of some derivates of 3-formyl-4-oxo-4H-pyridol,2-a-pyrim- idine. J Med Chem 1971; 14: 913–915.

    Google Scholar 

  46. Kaul CL, Grewal RS. Antihypertensive and monoamine oxidase inhibitory activity of 3-amino-2-oxazolidinone (3AO) and its condensation product with 2-substituted-3- formyl-4-oxo-4H pyrido l,2-apyrimidines. Biochem Pharmacol 1972; 21: 303–316.

    Google Scholar 

  47. Magyar K, Sátory E, Mészáros Z, Knoll J. Uj homopirimidazol származékok monoaminooxidáz-benitó hatása. Orvostudomány 1974; 25: 143.

    Google Scholar 

  48. Magyar K, Sátory E, Mészáros Z, Knoll J. The monoamine oxidase inhibitory effect of new homopyrimidazole dérivates. Med Biol 1974; 52: 384–389.

    Google Scholar 

  49. Sátory E, Mészáros Z, Magyar K, Knoll J. The monoamine oxidase inhibitory effect of new homopyrimidazole derivatives. Congr Hung Pharmacol Soc 1974 (Proa); 1976; 2: 43.

    Google Scholar 

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

    Google Scholar 

  51. Tipton KF. Kinetics and enzyme inhibition studies. In: Sandler M, editor. Enzyme Inhibitors as Drugs. London: Macmillan, 1980: 1–23.

    Google Scholar 

  52. Yu PH. Monoamine oxidase. In: Boulton AA, Baker GB, Yu PH, editors. Nurometh- ods Vol. 5. Neurotransmitter enzymes. New Jersey: Humana Press, 1986; 235–272.

    Google Scholar 

  53. Salach I J, Weyler W. Preparation of flavin containing aromatic amine oxidases of human placenta and beef liver. In: Colowick SP, Kaplan NO, editors. Methods in Enzymology. London: Academic Press, 1987; 142: 627–637.

    Google Scholar 

  54. Ansari GAS, Patel NT, Fritz RR, Abell CW. Purification of human platelet monoamine oxidase B by high performance liquid chromatography. J Liq Chromatogr 1983; 6: 1407–1419.

    Google Scholar 

  55. Youdim MBH, Tenne M. Assay and purification of liver monoamine oxidase. In: Colowick SP, Kaplan NO, editors. Methods in Enzymology. London: Academic Press, 1987; 142: 617–637.

    Google Scholar 

  56. Weissbach H, Smith TE, Daly JW, Witkop B, Udenfriend S. A rapid spectrophoto-metric assay of monoamine oxidase based on the rate of disappearance of kynuramine. J Biol Chem 1960; 235: 1160–1163.

    Google Scholar 

  57. Kraml M. Rapid microfluorometric determination of monoamine oxidase. Biochem Pharmacol 1965; 14: 1683–1685.

    Google Scholar 

  58. Tabor CW, Tabor H, Rosenthal SM. Purification of amine oxidase from beef plasma. J Biol Chem 1954; 208: 645–661.

    Google Scholar 

  59. Tenne M, Finberg JP, Youdim MBH, Ulitzur S. A new rapid and sensitive biolu-minescence assay for monoamine oxidase activity. J Neurochem 1985; 44: 1378–1384.

    Google Scholar 

  60. Wurtman RJ, Axelrod J. A sensitive and specific assay for the estimation of monoamine oxidase. Biochem Pharmacol 1963; 12: 1439–1440.

    Google Scholar 

  61. Tipton KF, Youdim MBH. Assay of monoamine oxidase. Ciba Found Symp (New Ser.) 1976; 39: 393–403.

    Google Scholar 

  62. Otsuka S, Kobayashi Y. Radioisotopic assay for monoamine oxidase determinations in human plasma. Biochem Pharmacol 1964; 13: 995–1006.

    Google Scholar 

  63. Inoue O, Tominaga T, Yamasaki T, Kinemuchi H. A new method for in vivo measurement of brain monoamine oxidase activity. Prog Neuropsychopharmacol Biol Psychiatry 1984; 8: 385–395.

    Google Scholar 

  64. Inoue O, Tominaga T, Yamasaki T, Kinemuchi H. Radioactive N,N-dimethyl-phenylethylamine: selective radiotracer for in vivo measurement of monoamine oxi-dase-B activity in the brain. J of Neurochem 1985; 44: 210–216.

    Google Scholar 

  65. Tominaga T, Inoue O, Suzuki K, Yamasaki T, Hirobe M. 13N-ß-phenethylamine (13NPEA): A prototype tracer for measurement of MAO-B activity in heart. Biochem Pharmacol 1987; 36: 3671–3675.

    Google Scholar 

  66. Severina IS. On the substrate-binding sites of the active centre of mitochondrial monoamine oxidase. Eur J Biochem 1973; 38: 239–246.

    Google Scholar 

  67. Severina IS. Multiplicity of mitochondrial monoamine oxidases and ways of selective blocking of the enzyme activity. Biokhimiia 1976; 41: 955–967.

    Google Scholar 

  68. Fowler CJ, Callingham BA, Mantle TJ, Tipton KF. The effect of lipophilic compounds upon the activity of rat liver mitochondrial monoamine oxidase-A and B. Biochem Pharmacol 1980; 29: 1177–1183.

    Google Scholar 

  69. Houslay MD, Tipton KF. A kinetic evaluation of monoamine oxidase activity in rat liver mitochondrial outer membranes. Biochem J 1974; 139: 645–652.

    Google Scholar 

  70. Roth JA. Inhibition of human brain type B monoamine oxidase by tricyclic psychoactive drugs. Mol Pharmacol 1978; 14: 164–171.

    Google Scholar 

  71. Edwards DJ, Burns MO. Effects of tricyclic antidepressants upon human platelet monoamine oxidase. Life Sci 1974; 15: 2045–2058.

    Google Scholar 

  72. Meyerson LR, McMurtrey KD, Davis VE. Neuroamine-derived alkaloids: substrate-preferred inhibitors of rat brain monoamine oxidase in vitro. Biochem Pharmacol 1976; 25: 1013–1020.

    Google Scholar 

  73. Bembenek ME, Abell CW, Chrisey LA, Rozwadowska MD, Gessner W, Brossi A. Inhibition of monoamine oxidase A and B by simple isoquinoline alkaloids: racemic and optically active 1,2,3,4-tetrahydro-, 3,4-dihydro-, and fully aromatic isoquinolines. J Med Chem 1990; 33: 147–152.

    Google Scholar 

  74. Freidinger RM, Williams PD, Tung RD, Bock MG, Pettibone DJ, Clineschmidt BV, et al. Vinblastine and vincristine are inhibitors of monoamine oxidase B. J Med Chem 1990; 33: 1845–1848.

    Google Scholar 

  75. Kaminski KA, Bodziony J, Kozielski J. Monitoring treatment of pulmonary carcinomas by serial determination of monoamine oxidase and diamine oxidase in blood serum. Arch Geschwulstforsch 1984; 54: 377–385.

    Google Scholar 

  76. Mantle TJ, Tipton KF, Garrett NJ. Inhibition of monoamine oxidase by amphetamine and related compounds. Biochem Pharmac 1976; 25: 2073–2077.

    Google Scholar 

  77. Kinemuchi H, Arai Y. Selective inhibition of monoamine oxidase A and B by two substrate-analogues. 5-fluoro-alpha-methyltryptamine and p-chloro-beta-methyl-phenethylamine. Res Commun Chem Pathol Pharmacol 1986; 54: 125–128.

    Google Scholar 

  78. Kim SK, Toyoshima Y, Arai Y, Kinemuchi H, Tadano T, Oyama K, et al. Inhibition of monoamine oxidase by two substrate-analogues with different preferences for 5-hy-droxytryptamine neurons. Neuropharmacology 1991; 30: 329–335.

    Google Scholar 

  79. Da Prada M, Kettler R, Keller HH, Cesura AM, Richards JG, Saura Marti J, et al. 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 Trans 1990; 29: 279–292.

    Google Scholar 

  80. Dostert P, Strolin-Benedetti M. Structure-modulated recognition of substrates and inhibitors by monoamine oxidase A and B. Biochemical Society Transactions, Amine Oxidases 1990; 19: 207–211.

    Google Scholar 

  81. Bench CJ, Price GW, Lammertsma AA, Cremmer JC, Luthra SK, Turon D, et al. Measurement of human cerebral monoamine oxidase type B (MAO-B) activity with positron emission tomography (PET): a dose ranging study with the reversible inhibitor Ro 19–6327. Eur J Clin Pharmacol 1991; 40: 169–173.

    Google Scholar 

  82. Kenny WC, Nagy J, Salach JI, Singer TP. Structure of the covalent Phenylhydrazine adduct of monoamine oxidase. In: Singer TP, editor. Monoamine oxidase: structure, function and altered function. New York: Academic Press, 1979: 25–37.

    Google Scholar 

  83. Abeles RH, Maycock AL. Suicide enzyme inactivators. Acc Chem Res 1976; 9: 313–319.

    Google Scholar 

  84. Fowler JC, Mantle TJ, Tipton KF. The nature of inhibition of rat liver monoamine oxidase types A and B by the acetylenic inhibitors clorgyline, l-deprenyl and pargyline. Biochem Pharmacol 1982; 31: 3555–3561.

    Google Scholar 

  85. Waldmeier PC, Feiner AE. Deprenyl: loss of selectivity for inhibition of B-type MAO after repeated treatment. Biochem Pharmacol 1978; 27: 801–802.

    Google Scholar 

  86. Ekstedt B, Magyar K, Knoll J. Does the B form selective monoamine oxidase inhibitor lose selectivity by long term treatment? Biochem Pharmacol 1979; 28: 919–923.

    Google Scholar 

  87. Csanda E, Tárczy M. Selegiline in the early and late phases of Parkinson’s disease. J Neural Trans 1987; 25(suppl.): 105–113.

    Google Scholar 

  88. Birkmayer W, Marton J, Hárs V, Reiederer P, Knoll J, Youdim MBH. l-Deprenyl increases the life expectancy of patients with Parkinson’s disease. In: Markey, Sanford P, editors. MPTP: neurotoxin producing a parkinsonian syndrome. Orlando, Fla: Academic Press, 1986; 599–606.

    Google Scholar 

  89. Tariot PN, Cohen RM, Sunderland T, Newhouse PA, Yount D, Mellow AM, et al. l-Deprenyl in Alzheimer’s disease: preliminary evidence for behavioral change with MAO-B inhibition. Arch Gen Psychiatry 1987; 44: 427–433.

    Google Scholar 

  90. Tariot PN, Sunderland T, Weingartner H, Murphy DL, Welkowitz JA, Thomson K, et al. Cognitive effects of l-deprenyl in Alzheimer’s disease. Psychopharmacology 1987; 91: 489–495.

    Google Scholar 

  91. Fejér E, Gaál J. Does deprenyl inhibit dopamine uptake? 18th FEBS Meeting: 1987 Jun 28-Jul 3; Ljubljana-Yugoslavia. Abstract: p. 273.

    Google Scholar 

  92. Cserhalmi M, Fejér E, Réffy A, Gaál J. Deprenyl binding site in human brain? In: Tucek S, Stipek S, Stastny F, Stipek S, 1986; N5: 320.

    Google Scholar 

  93. Knoll J, Ecsery Z, Magyar K, Sátory E. Novel (—)deprenyl-derived selective inhibitors of B-type monoamine oxidase. The relation of structure to their action. Biochem Pharmacol 1978; 27: 1739–1747.

    Google Scholar 

  94. Huebner CF, Donoghue EM, Plummer AJ, Furness PA. N-methyl-N-2-propynl-l-in- danamine. A potent monoamine oxidase inhibitor. J Med Chem 1966; 9: 830–832.

    Google Scholar 

  95. Maitre L. Monoamine oxidase inhibiting properties of SU-11,739 in the rat. Comparison with pargyline, tranylcypromine and iproniazid. J Pharm Exp Ther 1967; 157: 81–88.

    Google Scholar 

  96. Riederer P, Reynolds GP, Youdim MBH. Selectivity of MAO inhibitors in human brain and their clinical consequences. In: Youdin MBH, Paykel ES, editors. Monoamine oxidase inhibitors — The state of the art. Chichester: Wiley, 1981: 63–76.

    Google Scholar 

  97. Youdim MBH, Finberg JPM. MAO type B inhibitors as adjunct to L-dopa therapy. Adv in Neurol 1986; 45: 127–136.

    Google Scholar 

  98. Palfreyman MG, McDonald IA, Bey P, Danzin C, Zreika M, Lyles GA, et al. The rational design of suicide substrates of amine oxidases. Biochem Soc Trans 1986; 14: 410–413.

    Google Scholar 

  99. McDonald I, Palfreyman MG, Zreika M, Bey P. (Z)-2-(2,4-dichlorophenoxy)methyl-3- fluoroallylamine: a clorgyline analogue with surprising selectivity for monoamine oxidase type B. Biochem Pharmacol 1986; 35: 349–351.

    Google Scholar 

  100. Bey P, Fozard J, Lacoste JM, McDonald J, Zreika M, Palfreyman MG. (E)-2-(3,4- dimethoxyphenyl)-3-fluoroallylamine: A selective enzyme-activated inhibitor of type B monoamine oxidase. J Med Chem 1984; 27: 9–10.

    Google Scholar 

  101. Fozard JR, Palfreyman GM, Robin M, Zreika M. 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 1986; 87: 257–264.

    Google Scholar 

  102. Zreika M, Fozard JR, Dudley MW, Bey P, McDonald IA, Palfreyman MG. MDL 72.974A: a potent and selective enzyme activated irreversible inhibitor of monoamine oxidase type B with potential for use in Parkinson’s disease. J Neurol Trans 1989; 1: 243–254.

    Google Scholar 

  103. Silverman RB. Mechanism of inactivation of monoamine oxidase by trans-2-phenyl- cyclopropylamine and the structure of the enzyme-inactivator adduct. J Biol Chem 1983; 258: 14766–14769.

    Google Scholar 

  104. Silverman RB, Hiebert CK. Inactivation of monoamine oxidase A by the monoamine oxidase B inactivators 1-phenylcyclopropylamine, 1-benzylcyclopropy lamine, and N-cy- clopropyl-alpha-methylbenzyl amine. Biochemistry 1988; 27: 8448–8453.

    Google Scholar 

  105. Hermecz I, Mészáros Z. Pyridoll,2-apyrimidines; new chemical entities in medicinal chemistry. Med Res Rev 1988; 8: 203–230.

    Google Scholar 

  106. Danxin C, Collard P, Schirlin D. Selective inactivation on MAO-B by benzyl-dimethyl- silyl-methanamine in vitro. Biochem Biophys Res Com 1989; 160: 540–544.

    Google Scholar 

  107. Hallyday RP, Davis CS, Heotis JP, Pals DT, Watson EJ, Bickerton RK. Allenic amines: a new class of nonhydrazine MAO inhibitors. J Pharm Sci 1968; 53: 430–433.

    Google Scholar 

  108. White RL, Smith RA, Krantz A. Differential inactivation of mitochondrial monoamine oxidase by stereoisomers of allenic amines. Biochem Pharm 1983; 32: 3661–3664.

    Google Scholar 

  109. Sahlberg C, Ross SB, Fagervall I, Ask A-L, Claesson A. Synthesis of monoamine oxidase inhibitory activities of alpha allenic amines in vivo and in vitro. Different activities of two enantiomeric alienes. J Med Chem 1983; 26: 1036–1042.

    Google Scholar 

  110. Smith RA, White RL, Krantz A. Stereoisomers of allenic amines as inactivators of monoamine oxidase type B. Stereochemical probes of the active site. J Med Chem 1988; 31: 1558–1566.

    Google Scholar 

  111. Davis GC, Williams AC, Markey SP, Ebert MH, Caine ED, Reichert CM, et al. Chronic Parkinsonism secondary to intravenous injection of meperidine analogues. Psychiatry Res 1979; 1: 249–254.

    Google Scholar 

  112. Heikkila RE, Manzino L, Cabbat FS, Duvoisin RC. Protection against the dopaminergic neurotoxicity of l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine monoamine oxidase inhibitors. Nature 1984; 311: 467–469.

    Google Scholar 

  113. Chiba K, Trevor A, Castagnoli N, Jr. Metabolism of the neurotoxic tertiary amine, MPTP, by brain monoamine oxidase. Biochem Biophys Res Commun 1984; 120: 574–578.

    Google Scholar 

  114. Salach JI, Singer TP, Castagnoli N, Jr, Trevor A. Oxidation of the neurotoxic amine l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) by monoamine oxidases A and B and suicide inactivation of the enzymes by MPTP. Biochem Biophys Res Commun 1984; 125: 831–835.

    Google Scholar 

  115. Singer TP, Salach JI, Castagnoli N, Jr, Trevor A. Interactions of the neurotoxic amine l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine with monoamine oxidases. Biochem J 1986; 235: 785–789.

    Google Scholar 

  116. Tipton KF, McCrodden JM, Youdim MBH. Oxidation and enzyme-activated irreversible inhibition of rat liver monoamine oxidase-B by l-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP). Biochem J 1986; 240: 379–383.

    Google Scholar 

  117. Fuller RW, Hemrick-Luecke SK. Inhibition of types A and B monoamine oxidase by l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine. J Pharm Exp Ther 1985; 232: 696- 701.

    Google Scholar 

  118. Peterson LA, Caldera PS, Trevor A, Chiba K, Castagnoli N, Jr. Studies on the l-methyl-4-phenyl-2,3-dihydropyridinium species 2,3-MPDP+, the monoamine oxidase catalyzed oxidation product of the nigrostriatal toxin l-methyl-4-phenyl-l,2,3,6-tetrahy- dropyridine (MPTP). J Med Chem 1985; 28: 1432–1436.

    Google Scholar 

  119. Singer TP, Salach JI, Castagnoli N, Jr, Trevor A. Interactions of the neurotoxic amine l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine with monoamine oxidases. Biochem J 1986; 235: 785–789.

    Google Scholar 

  120. Singer TP, Ramsay R. The interaction of monoamine oxidases with tertiary amines. Biochemical Society Transactions, Amine Oxidases 1990; 19: 211–215.

    Google Scholar 

  121. Dostert PL, Strolin-Benedetti S, Tipton KF. Interaction of monoamine oxidase with substrate and inhibitors. Med Res Rev 1989; 9: 45–89.

    Google Scholar 

  122. Tipton KF, Fowler CJ, McRodden JM, Strolin-Benedetti M. The enzyme-activated irreversible inhibition of type-B monoamine oxidase by 3-4-(3-chlorophenyl)me- thoxyphenyl-5- (methyl-amino)-methy-2-oxazolidinone methansulphonate (compound MD 780236) and the enzyme-catalyzed oxidation of this compound as competing reactions. Biochem J 1983; 209: 235–242.

    Google Scholar 

  123. Dostert P, Strolin-Benedetti M, Guffroy C. Different stereoselective inhibition of monoamine oxidase-B by the R- and S-enantiomers of MD 780236. J Pharm Pharmacol 1983; 35: 161–165.

    Google Scholar 

  124. Tenne M, Youdim BH. MAO-inhibiting drugs: stereochemical aspects. In: Smith D, editor. CRC Handbook of Stereoisomers: Drugs in Psychopharmacology; Boca Raton, FL: CRC, 1984; 285–296.

    Google Scholar 

  125. Finnegan KT, Skratt JJ, Irwin I, DeLanney LE, Langston JW. Protection against DSP-4 induced neurotoxicity by deprenyl is not related to its inhibition of MAO-B. Eur J Pharmacol 1990; 184: 119–126.

    Google Scholar 

  126. Tipton KF, McCrodden JM, Kalir AS, Youdim MBH. Inhibition of rat liver monoamine oxidase by alpha-methyl- and N-propargyl-amine derivatives. Biochem Pharmacol 1982; 31: 1251–1255.

    Google Scholar 

  127. Heikkila RE, Davoison JP, Finberg M, Youdim MBH. Prevention of MPTP-induced neurotoxicity by AGN-1133 and AGN-1135, selective inhibitors of monoamine oxidase- B. Eur J Pharmacol 1985; 116: 313–317.

    Google Scholar 

  128. Swett LR, Martin WB, Taylor JD, Everett GM, Wykers AA, Gladish YC. Structure-activity relations in the pargyline series. Ann NY Acad Sci 1963; 107: 891–898.

    Google Scholar 

  129. Karoum F. N-Propargylbenzylamine, a major metabolite of pargyline, is a potent inhibitor of monoamine oxidase type-B in rats in vivo: a comparison with deprenyl. Br J Pharmacol 1987; 90: 335–345.

    Google Scholar 

  130. Martin YC, Martin WB, Taylor JD. Regression analysis of the relationship between physical properties and the in vitro inhibition of monoamine oxidase by propynyl- amines. J Med Chem 1975; 18: 883–888.

    Google Scholar 

  131. Ecsery Z, Knoll J, Somfai É, Török Z, Szinnyei É, Mozsolits K. Phenylizopropylamine derivative. PCT Int Appl WO 85 05,617 (1986; CA 105: 78632).

    Google Scholar 

  132. Plenevaux A, Dewey SL, Fowler JS, Guillaume M, Wolf AP. Synthesis of (R)-(-) and (S)-(+)-4-fluorodeprenyl and (R)-(-) and (S)-(+)-AT-nC-methyl-4-fluorodeprenyl and positron emission tomography studies in baboon brain. J Med Chem 1990; 33: 2015–2019.

    Google Scholar 

  133. Kettler R, Keller HH, Bonetti EP, Wyss PC, DaPrada M. Ro 16–6491: a new highly selective and reversible MAO-B inhibitor. J Neurochem 1985; 44: (Suppl.) S94.

    Google Scholar 

  134. Fuller RW, Henrick SK, Mills J. Inhibition of monoamine oxidase by N-phenacil-cyclo- propylamine. Biochem Pharmacol 1978; 27: 2255–2261 C.

    Google Scholar 

  135. Colpaert FC, Niemegeers, Carlos JE, Janssen PAJ. Evidence that a preferred substrate for type-B monoamine oxidase mediates stimulus properties of MAO inhibitors: a possible role for beta-phenylethyl-amine in the cocaine cue. Pharm Biochem Behav 1980; 13: 513–517.

    Google Scholar 

  136. Roba J. Milacimide: a novel anti-convulsant. In: Meldum BS, Porter RR, editors. New anticonvulsant drugs. London: Libbey J and Co., 1966; 179–190.

    Google Scholar 

  137. Buckman TD, Eiduson S, Boscia R. Investigation of the mechanism of selective inhibition of type-B mitochondrial monoamine oxidase by phoshatidylserine. Biochem Pharmacol 1983; 32: 3639–3647.

    Google Scholar 

  138. Strolin Benedetti M, Dostert P. Stereochemical aspects of MAO interaction: reversible and selective inhibitors of monoamine oxidase. Trends in Pharm Sci 1985; 6: 246–251.

    Google Scholar 

Download references

Authors
  1. J. Gaál
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. I. Hermecz
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Dept. of Pharmacology, ASTA Medica AG, Weismüllerstrasse 45, D-6000, Frankfurt/Main 1, Germany

    I. Szelenyi

Rights and permissions

Reprints and permissions

Copyright information

© 1993 Springer Basel AG

About this chapter

Cite this chapter

Gaál, J., Hermecz, I. (1993). Medicinal Chemistry of Present and Future MAO-B Inhibitors. In: Szelenyi, I. (eds) Inhibitors of Monoamine Oxidase B. Milestones in Drug Therapy. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-6348-3_4

Download citation

  • DOI: https://doi.org/10.1007/978-3-0348-6348-3_4

  • Publisher Name: Birkhäuser, Basel

  • Print ISBN: 978-3-0348-6349-0

  • Online ISBN: 978-3-0348-6348-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation