Monoamine Oxidase Inhibitors as Antidepressants

  • N. S. Kline
  • T. B. Cooper
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 55 / 1)


The history of monoamine oxidase inhibitor (MAOI) use in psychiatry is a curious one and far from complete. The inspiration for our own use derived from the work of Chessin et al. (1956) who found that “marsalinizing” (treating with Marsilid, i.e., iproniazid) an animal before administering reserpine produced a paradoxical effect1. The animal rather than becoming sedated became hyperalert and active. Scott described these findings during a visit to Warner Laboratories as part of a discussion which dealt with the mode of action of reserpine. The possibility of using this combination to activate retarded schizophrenic patients and to treat depression suggested itself.


Depressed Patient Monoamine Oxidase Biogenic Amine Monoamine Oxidase Inhibitor Broad Bean 
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  1. Ananth, J., Luchins, D.: A review of combined tricyclic and MAOI therapy. Compr. Psychiatry 18, 221–230 (1977)PubMedCrossRefGoogle Scholar
  2. Asatoor, A.M., Levi, A.J., Milne, M.D.: Tranylcypromine and cheese. Lancet 2, 733–734 (1963)PubMedCrossRefGoogle Scholar
  3. Axelrod, J.: O-methylation of epinephrine and other catechols in vitro and in vivo. Science 126, 400 (1957)PubMedCrossRefGoogle Scholar
  4. Ayd, F.J.: A preliminary report on marsilid. Am. J. Psychiatry 114, 459 (1957)PubMedGoogle Scholar
  5. Bailey, S.D., Bucci, L., Gosline, E., Kline, N.S., Park, I.H., Rochlin, D., Saunders, J.C., Vaisberg, M.: Comparison of iproniazid with other amine oxidase inhibitors, including W-1544, JB-516, R04-1018, and R05-0700. Ann. N.Y. Acad. Sci. 80, 652–668 (1959)PubMedCrossRefGoogle Scholar
  6. Baldessarini, R.J.: Mood drugs. In: Disease-A-Month. Dowling, H.F. (ed.), Vol. 24, 2., Chicago: Year Book Medical Publishers 1977Google Scholar
  7. Berger, P.A., Barchas, J.D.: Monoamine oxidase inhibitors. In: Psychotherapeutic drugs. Usdin, E., Forrest, I. (eds.). New York: Dekker 1977Google Scholar
  8. Biel, J.H., Bopp, B.: Monoamine oxidase inhibitor antidepressants. In: Psychopharmacological agents. Gordon, M. (ed.), pp. 302–309. New York: Academic Press 1974Google Scholar
  9. Birkmayer, W., Yahr, M. (eds.): Deprenyl, an inhibitor of MAO-type B in the treatment of Parkinsonism. J. Neural. Transm. 43, 3–4 (1978)Google Scholar
  10. Blackwell, B., Marley, E., Ryle, A.: Hypertensive crisis associated with monoamine-oxidase inhibitors. Lancet 1, 722–723 (1964)PubMedCrossRefGoogle Scholar
  11. Brodie, B.B., Pletscher, A., Shore, P.A.: Possible role of serotonin in brain function and in reserpine action. J. Pharmacol. Exp. Ther. 116, 9 (1956)Google Scholar
  12. Bunney, W.E., Davis, J.M.: Norepinephrine in depressive reactions. A review. Arch. Gen. Psychiatry 13, 483–494 (1965)Google Scholar
  13. Burn, J.H., Philpot, F.J., Trendelenburg, U.: Effect of denervation on enzymes in iris and blood vessels. Br. J. Pharmacol. 9, 423–428 (1954)Google Scholar
  14. Chessin, M., Dubnick, B., Kramer, E.R., Scott, C.C.: Modifications of pharmacology of reser-pine and serotonin by iproniazid. Fed. Proc. 15, 409 (1956)Google Scholar
  15. Cooper, A.J., Ashcroft, G.: Potentiation of insulin hypoglycaemia by MAOI antidepressant drugs. Lancet 1, 407–409 (1966)PubMedCrossRefGoogle Scholar
  16. Crane, G.E.: Further studies on iproniazid phosphate. Isonicotinil-isopropylhydrazine phosphate Marsilid. J. Nerv. Ment. Dis. 124, 322–331 (1956)PubMedCrossRefGoogle Scholar
  17. Crane, G.E.: The psychiatric side-effects of iproniazid. Am. J. Psychiatry 112, 494–501 (1956)PubMedGoogle Scholar
  18. Davidson, J., McCleod, M.N., Blum, M.R.: Acetylation phenotype, platelet monoamine oxidase inhibition, and the effectiveness of phenelzine in depression. Am. J. Psychiatry 135, 467–469 (1978)PubMedGoogle Scholar
  19. Dunleavy, D.L.F., Oswald, I.: Phenelzine, mood response and sleep. Arch. Gen. Psychiatry 28, 353–356 (1973)PubMedGoogle Scholar
  20. Escobar, J.I., Schiele, B.C., Zimmermann, R.: The tranylcypromine isomers: A controlled clinical trial. Am. J. Psychiatry 131, 1025–1026 (1974)PubMedGoogle Scholar
  21. Evans, D.A.P., Manley, K.A., McKusick, V.A.: Genetic control of isoniazid metabolism in man. Br. Med. J. 2, 485–491 (1960)PubMedCrossRefGoogle Scholar
  22. Evans, D.A.P., Davison, K., Pratt, R.T.C.: The influence of acetylator phenotype on the effects of treating depression with phenelzine. Clin. Pharmacol. Ther. 6, 430–435 (1965)PubMedGoogle Scholar
  23. Fisher, M.M., Mammlok, E.R., Tendlau, A., Tebrock, H.E., Drumm, A.E., Spiegelman, A.: Isonicotinic acid hydrazide and its derivatives in tuberculosis: An evaluation of the side-effects in relation to peripheral circulation; preliminary report. 52, 1519–1527 (1952)Google Scholar
  24. Fowler, C.J., Callingham, B.A., Mantle, T.J., Tipton, K.F.: Monoamine oxidase A and B: A useful concept? Biochem. Pharmacol. 27, 97–101 (1978)CrossRefGoogle Scholar
  25. Franzen, F., Eysell, K. (eds.): Biologically active amines found in man. Oxford: Pergamon Press 1969Google Scholar
  26. Friend, D.G., Zileli, M.S., Hamlin, J.T., Reutter, F.W.: The effect of iproniazid on the inacti-vation of norepinephrine in the human. J. Clin. Exp. Psychopathol. 19, 61–71 (1958)PubMedGoogle Scholar
  27. Fuller, R.W.: Selective inhibition of monoamine oxidate. Adv. Biochem. Psychopharm. 5, 339–354 (1972)Google Scholar
  28. Fuller, R.W.: Selectivity among monoamine oxidase inhibitors and its possible importance for development of antidepressant drugs. Prog. Neuropsychopharmacol. 2, 303–311 (1978)CrossRefGoogle Scholar
  29. Fuller, R.W., Roush, B.W.: Procaine hydrochloride as a monoamine oxidase inhibitor: Implications for geriatric therapy. J. Am. Geriatr. Soc. 25, 90–93 (1977)PubMedGoogle Scholar
  30. Gaddum, J.H., Kwiatkowski, H.: The action of ephedrine. J. Physiol. (Lond.) 94, 87–100 (1938)PubMedGoogle Scholar
  31. Goodman, L.S., Gilman, A.: The pharmacological basis of therapeutics. 2nd ed., p. 517. New York: Macmillan 1965Google Scholar
  32. Hendley, E.D., Snyder, S.H.: Relationship between the action of monoamine oxidase inhibitors on the noradrenaline uptake system and their antidepressant efficacy. Nature 220, 1330–1331 (1968)PubMedCrossRefGoogle Scholar
  33. Hodge, J.V., Nye, E.R., Emerson, G.W.: Monoamine-oxidase inhibitors, broad beans, and hypertension. Lancet 1, 1108 (1964)PubMedCrossRefGoogle Scholar
  34. Horwitz, D., Goldberg, L.I., Sjoerdsma, A.: Increased blood pressure responses to dopamine and norepinephrine produced by monoamine oxidase inhibitors in man. J. Lab. Clin. Med. 56, 747–753 (1960)PubMedGoogle Scholar
  35. Horwitz, D., Lovenberg, W., Engelman, K., Sjoerdsma, A.: Monoamine oxidase inhibitors, tyramine, and cheese. J. Am. Med. Assoc. 188, 1108 (1964)Google Scholar
  36. Houslay, M.D., Garrett, N.J., Tipton, K.F.: Mixed substrate experiments with human brain monoamine oxidase. Biochem. Pharmacol. 23, 1937–1944 (1974)Google Scholar
  37. Houslay, M.D., Tipton, K.F., Youdim, M.B.H.: Minireview Multiple forms of monoamine oxidase: Fact and artefact. Life Sci. 19, 467–478 (1976)PubMedCrossRefGoogle Scholar
  38. Jarvik, M.: Drugs used in the treatment of psychiatric disorders. In: The pharmacological basis of therapeutics. 5 th ed. Goodman, L.S., Gilman, A. (eds.), pp. 151–203. New York: MacMillan 1970Google Scholar
  39. Johnston, J.P.: Some observations upon a new inhibitor of monoamine oxidase in brain tissue. Biochem. Pharmacol. 17, 1285–1297 (1968)PubMedCrossRefGoogle Scholar
  40. Johnstone, E.C., Marsh, W.: Acetylator status and response to phenelzine in depressed patients. Lancet 1, 567–570 (1973)PubMedCrossRefGoogle Scholar
  41. Kamman, G.R., Freeman, J.G., Lucero, R.J.: The effect of l-isonicotynil-2-isopropyl hydrazine (IIH) on the behavior of long-term mental patients. J. Nerv. Ment. Dis. 118, 391–407 (1953)PubMedCrossRefGoogle Scholar
  42. Kiloh, L.G., Child, J.P., Latner, G.: A controlled trial of iproniazid in the treatment of endogenous depression. J. Ment. Sci. 106, 1139–1144 (1960)PubMedGoogle Scholar
  43. Kline, N.S.: Present status of psychopharmacological Research: Includes Loomer, H., Saunders, J.C., Kline, N.S.: Iproniazid, an amine oxidase inhibitor, as an example of a psychic energizer. Hearings before the subcommittee of the Committee on Appropriations, United States Senate, 85th Congress, 1st Session on H.R. 6287, pp. 1372–1390, May 9, 1957. Washington, D.C.: U.S. Government Printing Office 1957Google Scholar
  44. Kline, N.S.: Quoted in: Berger, P.A., Barchas, J.D. In: Psychotherapeutic drugs. Usdin, E., Forrest, I. (eds.), p. 1175. New York: Dekker 1977Google Scholar
  45. Kline, N.S., Sacks, W.: Relief of depression within one day using an M.A.O. inhibitor and intravenous 5-HTP. Am. J. Psychiatry 120, 274–275 (1963)PubMedGoogle Scholar
  46. Kline, N.S., Sacks, W.: Treatment of depression with an MAO inhibitor followed by 5-HTP — an unfinished research project. Presented at Symposium on Biogenic Amines and Affective Disorders. London. Jan. 18–21, 1979Google Scholar
  47. Kline, N.S., Alexander, S.F., Chamberlain, A.: In: Psychotropic drugs. Manual for emergency management overdosage. New Jersey: Medical Economics Company 1974Google Scholar
  48. Kline, N.S., Sacks, W., Simpson, G.M.: Further studies on: One day treatment of depression with 5-HTP. Am. J. Psychiatry 121, 379–381 (1964)PubMedGoogle Scholar
  49. Kopin, I.J., Axelrod, J.: The role of monoamine oxidase in the release and metabolism of norepinephrine. Ann. N.Y. Acad. Sci. 107, 848 (1963)PubMedCrossRefGoogle Scholar
  50. Krikler, D.M., Lewis, B.: Dangers of natural foodstuffs. Lancet 1, 1166 (1965)CrossRefGoogle Scholar
  51. Lader, M.: Antianxiety drugs: Clinical pharmacology and therapeutic use. Drugs 12, 362–373 (1976)PubMedCrossRefGoogle Scholar
  52. Leonard, B.E.: Some effects of mianserin on monoamine metabolism in the rat brain. Br. J. Clin. Pharmacol. 5, 11S–12S (1978)PubMedGoogle Scholar
  53. Loomer, H.P., Saunders, J.C., Kline, N.S.: A clinical and pharmacodynamic evaluation of iproniazid as a psychic energizer. Psychiatr. Res. Rep. 8, 129–141 (1958)Google Scholar
  54. Maclean, R., Nicholson, W.J., Pare, C.M.B., Stacey, R.S.: Effect of monoamine-oxidase inhibitors on the concentrations of 5-hydroxytryptamine in the human brain. Lancet 2, 205–208 (1965)CrossRefGoogle Scholar
  55. Marley, E.: Monoamine oxidase inhibitors. In: Drug interactions. Grahame-Smith, D.G. (ed.), pp. 178–194. Baltimore: University Park Press 1977Google Scholar
  56. Marshall, E.F., Mountjoy, C.O., Campbell, I.C., Garside, R.F., Leitch, I.M., Roth, M.: The influence of acetylator phenotype on the outcome of treatment with phenelzine, in a clinical trial. Br. J. Clin. Pharmacol. 6, 247–254 (1978)PubMedGoogle Scholar
  57. Mielke, D.H.: Adverse reactions of thymoleptics. In: Depression: Behavioral, biochemical, diagnostic and treatment concepts. Gallant, D.M., Simpson, G.M. (eds.), pp. 273–308. Stuttgart: Spectrum Publications 1976Google Scholar
  58. Morris, J.B., Beck, A.T.: The efficacy of antidepressant drugs. A review of research (1958 to 1972). Arch. Gen. Psychiatry 30, 667–674 (1974)PubMedGoogle Scholar
  59. Murphy, D.L.: The behavioral toxicity of monoamine oxidase-inhibiting antidepressants. Adv. Pharmacol. Chemother. 14, 71–105 (1977)PubMedCrossRefGoogle Scholar
  60. Murphy, D.L., Donnelly, C.H.: Monoamine oxidase in man: enzyme characteristics in platelets, and other human tissue. In: Neuropsychopharmacology of monoamines and their regulatory enzymes. Usdin, E. (ed.), pp. 71–85. New York: Raven Press 1974Google Scholar
  61. Murphy, D.L., Belmaker, R., Wyatt, R.J.: Monoamine oxidase in schizophrenia and other behavioral disorders. J. Psychiatr. Res. 11, 221–247 (1974)PubMedCrossRefGoogle Scholar
  62. Neff, N.H., Yang, H.-Y.T.: Life Sci. 14, 2061–2074 (1974)PubMedCrossRefGoogle Scholar
  63. Nelson, S.D., Mitchell, J.R., Timbrell, J.A., et al: Isoniazid and iproniazid: Activation of metabolites to toxic intermediates in man and rat. Science 193, 901–903 (1976)PubMedCrossRefGoogle Scholar
  64. Nies, A., Robinson, D.S., Lamborn, K.R., Lampert, R.P.: Genetic control of platelet and plasma monoamine oxidase activity. Arch. Gen. Psychiatry 28, 834–838 (1973)PubMedGoogle Scholar
  65. Nies, A., Robinson, D.S., Harris, L.S., Lamborn, K.R.: Comparison of monoamine oxidase substrate activity in twins, schizophrenics, depressives, and controls. In: Advances in bio-chem. psychopharmacol. Neuropsychopharmacology of monoamine and their regulatory enzymes. Usdin, E. (ed.). New York: Raven Press 1974Google Scholar
  66. Ostow, M., Kline, N.S.: The psychic action of reserpine and chlorpromazine. In: Psychophar-macology frontiers. Kline, N.S. (ed.), Appendix, pp. 481–513. Boston, Mass.: Little, Brown & Co. 1959Google Scholar
  67. Paykel, E.S.: Classification of depressed patients: A cluster analysis derived grouping. Br. J. Psychiatry 118, 275–288 (1971)PubMedCrossRefGoogle Scholar
  68. Pletscher, A., Shore, P.A., Brodie, B.B.: Serotonin as a mediator of reserpine action in brain. J. Pharmacol. Exp. Ther. 116, 84–89 (1956)PubMedGoogle Scholar
  69. Raskin, A.: Adverse reactions to phenelzine: Results of a nine-hospital depression study. J. Clin. Pharmacol. 12, 22–25 (1972)Google Scholar
  70. Robinson, D.S., Lovenberg, W., Keiser, H., Sjoerdsma, A.: Effects of drugs on human blood platelet and plasma amine oxidase activity in vitro and in vivo. Biochem. Pharmacol. 17, 109–119(1968)PubMedCrossRefGoogle Scholar
  71. Robinson, D.S., Nies, A., Ravaris, C.L., Ives, J.O., Bartlett, D.: Clinical psychopharmacology of phenelzine: MAO activity and clinical response. In: Psychopharmacology: A generation of progress. Lipton, M.A., DiMascio, A., Killam, K.F. (eds.). New York: Raven Press 1978Google Scholar
  72. Rosloff, B.N., Davis, J.M.: Effect of iprindole on norepinephrine turnover and transport. Psychopharmacologia (Berl.) 40, 53–64 (1974)CrossRefGoogle Scholar
  73. Saunders, J.C., Radinger, N., Rochlin, D., Kline, N.S.: Treatment of depressed and regressed patients with iproniazid and reserpine. Dis. Nerv. Syst. 20, 1–8 (1959)Google Scholar
  74. Schiele, B.C.: The parnate specific patient. Minn. Med. 48, 355–357 (1965)Google Scholar
  75. Schildkraut, J.J.: The catecholamine hypothesis of affective disorders: A review of supporting evidence. Am. J. Psychiatry 122, 509–522 (1965)PubMedGoogle Scholar
  76. Schuckit, M., Robins, E., Feighner, J.: Tricyclic antidepressants and monoamine oxidase inhibitors: Combination therapy in the treatment of depression. Arch. Gen. Psychiatry 24, 509–514 (1971)PubMedGoogle Scholar
  77. Selikoff, I.J., Robitzvek, E.H., Ornstein, G.G.: Toxicity of hydrazine derivatives of isonicotinic acid in the chemotherapy of human tuberculosis. Q. Bull. Sea View Hosp. 13, 17–26 (1952)Google Scholar
  78. Shaw, D.M.: The practical management of affective disorders. Br. J. Psychiatry 130, 432–451 (1977)PubMedCrossRefGoogle Scholar
  79. Shopsin, B., Kline, N.S.: Monoamine oxidase inhibitors: Potential for drug abuse. Biol. Psychiatry 11, 451–456 (1976)Google Scholar
  80. Sjoqvist, F.: SPIIn: Monoamine oxidase inhibitors: Relationship between pharmacological and clinical effects. Cheymol, J., Boissier, J.R., Vol. 10. New York: Pergamon Press 1968Google Scholar
  81. Smith, J.A.: The use of the isopropyl derivative of isonicotinylhydrazine (marsilid) in the treatment of mental disease; A preliminary report. Am. Practitioner 4, 519–520 (1953)PubMedGoogle Scholar
  82. Spector, S., Hirsch, C.W., Brodie, B.B.: Association of behavioral effects of pargyline, a non-hydrazide monoamine oxidase inhibitor with increase in brain norepinephrine. Int. J. Neuropharmacol. 2, 81–93 (1963)CrossRefGoogle Scholar
  83. Spiker, D.G., Pugh, D.D.: Combining tricyclic and monoamine oxidase inhibitor antidepressants. Arch. Gen. Psychiatry 33, 828–830 (1976)PubMedGoogle Scholar
  84. Tyrer, P., Candy, J., Kelly, D.: Phenelzine in phobia anxiety: A controlled trial. Psychol. Med. 3, 120–124 (1973)PubMedCrossRefGoogle Scholar
  85. Usdin, E. (ed.): Neuropsychopharmacology of monoamines and their regulatory enzymes. Advances in biochemical psychopharmacology, Vol. 12. New York: Raven Press 1974Google Scholar
  86. Von Bruecke, F., Hornykiewicz, O., Sigg, E.B.: Monoamine oxidase inhibitors. In: The pharmacology of psychotherapeutic drugs. pp. 78–102. Berlin, Heidelberg, New York: Springer 1969Google Scholar
  87. West, E.D., Dally, P.J.: Effects of iproniazid in depressive syndromes. Br. Med. J. 1, 1491–1494 (1959)PubMedCrossRefGoogle Scholar
  88. Yang, H.-Y.T., Neff, N.H.: B-phenylethylamine: A specific substrate for type B monoamine oxidase of brain. J. Pharmacol. Exp. Ther. 187, 365–371 (1973)PubMedGoogle Scholar
  89. Youdim, M.B.: Multiple forms of mitochondrial monoamine oxidase. Br. Med. Bull. 29, 120–122 (1973)PubMedGoogle Scholar
  90. Zeller, E.A., Barsky, J.: In vivo inhibition of liver and brain monoamine oxidase by 1-isonicotinyl-2-isopropyl hydrazine. Proc. Soc. Exp. Biol. Med. 81, 459–461 (1952)PubMedGoogle Scholar

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  • N. S. Kline
  • T. B. Cooper

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