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Tranylcypromine

New perspectives on an “old” drug

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Abstract

The irreversible inhibitor of monoamine oxidase, tranylcypromine, is a potent antidepressant, but its use is limited to special indications due to side effects and dietary restrictions. The antidepressant action of tranylcypromine is not completely explainable by its effects on monoamine oxidase. Tranylcypromine also leads to an increase in brain trace amines, which are believed to play a key role in the pathophysiology of depression. It also affects other pathophysiological pathways associated with depression. Tranylcypromine treatment leads to an up-regulation of GABAB-receptors and modulates the phospholipid metabolism, which is essential for normal brain function. These findings implicate that the efficacy of tranylcypromine as an antidepressant may be due to its multiple actions within the human brain.

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References

  1. Altar CA, Laeng P, Jurata LW, Brockman JA, Lemire A, Bullard J, Bukhman YV, Young TA, Charles V, Palfreyman MG (2004) Electroconvulsive seizures regulate gene expression of distinct neurotrophic signaling pathways. J Neurosci 24:2667–2677

    Article  PubMed  CAS  Google Scholar 

  2. Baker GB, Coutts RT, Greenshaw AJ (2000) Neurochemical and metabolic aspects of antidepressants: an overview. J Psychiat Neurosci 25:481–496

    CAS  Google Scholar 

  3. Baker GB, Hampson DR, Coutts RT, Micetich RG, Hall TW, Rao TS (1986) Detection and quantitation of a ring-hydroxylated metabolite of the antidepressant drug tranylcypromine. J Neural Transm 65:233–243

    Article  PubMed  CAS  Google Scholar 

  4. Baker GB, Martin IL, Mtichel PR (1977) The effects of some indolalkylamines on the uptake and release of 5-hydroxytryptamine in rat striatum [proceedings]. Br J Pharmacol 61:151P–152P

    PubMed  CAS  Google Scholar 

  5. Baker GB, Urichuk LJ, McKenna KF, Kennedy SH (1999) Metabolism of monoamine oxidase inhibitors. Cell Mol Neurobiol 19:411–426

    Article  PubMed  CAS  Google Scholar 

  6. Bazan NG (2003) Synaptic lipid signaling: significance of polyunsaturated fatty acids and platelet-activating factor. J Lipid Res 44:2221–2233

    Article  PubMed  CAS  Google Scholar 

  7. Berlin I, Said S, Spreux-Varoquaux O, Olivares R, Launay JM, Puech AJ (1995) Monoamine oxidase A and B activities in heavy smokers. Biol Psychiat 38:756–761

    Article  PubMed  CAS  Google Scholar 

  8. Borowsky B, Adham N, Jones KA, Raddatz R, Artymyshyn R, Ogozalek KL, Durkin MM, Lakhlani PP, Bonini JA, Pathirana S, Boyle N, Pu X, Kouranova E, Lichtblau H, Ochoa FY, Branchek TA, Gerald C (2001) Trace amines: identification of a family of mammalian G protein-coupled receptors. Proc Natl Acad Sci USA 98:8966–8971

    Article  PubMed  CAS  Google Scholar 

  9. Branchek TA, Blackburn TP (2003) Trace amine receptors as targets for novel therapeutics: legend, myth and fact. Curr Opin Pharmacol 3:90–97

    Article  PubMed  CAS  Google Scholar 

  10. Breslau N, Novak SP, Kessler RC (2004) Daily smoking and the subsequent onset of psychiatric disorders. Psychol Med 34:323–333

    Article  PubMed  CAS  Google Scholar 

  11. Breslau N, Novak SP, Kessler RC (2004) Psychiatric disorders and stages of smoking. Biol Psychiat 55:69–76

    Article  PubMed  Google Scholar 

  12. Calverley DG, Baker GB, Coutts RT, Dewhurst WG (1981) A method for measurement of tranylcypromine in rat brain regions using gas chromatography with electron capture detection. Biochem Pharmacol 30:861–867

    Article  PubMed  CAS  Google Scholar 

  13. Cohen RM, Ebstein RP, Daly JW, Murphy DL (1982) Chronic effects of a monoamine oxidase-inhibiting antidepressant: decreases in functional alpha-adrenergic autoreceptors precede the decrease in norepinephrine-stimulated cyclic adenosine 3′:5′-monophosphate systems in rat brain. J Neurosci 2:1588–1595

    PubMed  CAS  Google Scholar 

  14. Davis BA, Boulton AA (1994) The trace amines and their acidic metabolites in depression – an overview. Prog Neuropsychopharmacol Biol Psychiat 18:17–45

    Article  CAS  Google Scholar 

  15. Draper AJ, Madan A, Parkinson A (1997) Inhibition of coumarin 7-hydroxylase activity in human liver microsomes. Arch Biochem Biophys 341:47–61

    Article  PubMed  CAS  Google Scholar 

  16. Fergusson DM, Goodwin RD, Horwood LJ (2003) Major depression and cigarette smoking: results of a 21-year longitudinal study. Psychol Med 33:1357–1367

    Article  PubMed  CAS  Google Scholar 

  17. Fitton A, Faulds D, Goa KL (1992) Moclobemide. A review of its pharmacological properties and therapeutic use in depressive illness. Drugs 43:561–596

    PubMed  CAS  Google Scholar 

  18. Fitzgerald DH, Tipton KF (2002) Inhibition of monoamine oxidase modulates the behaviour of semicarbazide-sensitive amine oxidase (SSAO). J Neural Transm 109:251–265

    Article  PubMed  CAS  Google Scholar 

  19. Fitzgerald DH, Tipton KF, Lyles GA (1998) Studies on the behaviour of semicarbazide-sensitive amine oxidase in Sprague-Dawley rats treated with the monoamine oxidase inhibitor tranylcypromine. J Neural Transm Suppl 52:259–264

    PubMed  CAS  Google Scholar 

  20. Frazer A, Lucki I (1982) Antidepressant drugs: effects on beta-adrenergic and serotonineregic receptors. Adv Biochem Psychopharmacol 31:69–90

    PubMed  CAS  Google Scholar 

  21. Goodnough DB, Baker GB (1994) Comparisons of the actions of high and low doses of the MAO inhibitor tranylcypromine on 5-HT2 binding sites in rat cortex. J Neural Transm Suppl 41:127–134

    PubMed  CAS  Google Scholar 

  22. Gordon JL, Pearson JD, MacIntyre DE (1979) Effect of prostaglandin E2 on prostacyclin production by endothelial cells. Nature 278:480

    Article  PubMed  CAS  Google Scholar 

  23. Greenshaw AJ, Nazarali AJ, Rao TS, Baker GB, Coutts RT (1988) Chronic tranylcypromine treatment induces functional alpha 2-adrenoceptor down-regulation in rats. Eur J Pharmacol 154:67–72

    Article  PubMed  CAS  Google Scholar 

  24. Haag M (2003) Essential fatty acids and the brain. Can J Psychiat 48:195–203

    Google Scholar 

  25. Hampson DR, Baker GB, Coutts RT (1986) A comparison of the neurochemical properties of the stereoisomers of tranylcypromine in the central nervous system. Cell Mol Biol 32:593–599

    PubMed  CAS  Google Scholar 

  26. Heller B, Fischer E, Martin R (1976) Therapeutic action of d-phenylalanine in Parkinson’s disease. Arzneimittelforschung 26:577–579

    PubMed  CAS  Google Scholar 

  27. Hong SL, Carty T, Deykin D (1980) Tranylcypromine and 15-hydroperoxyarachidonate affect arachidonic acid release in addition to inhibition of prostacyclin synthesis in calf aortic endothelial cells. J Biol Chem 255:9538–9540

    PubMed  CAS  Google Scholar 

  28. Horrobin DF (2001) Phospholipid metabolism and depression: the possible roles of phospholipase A2 and coenzyme A-independent transacylase. Hum Psychopharmacol 16:45–52

    Article  PubMed  CAS  Google Scholar 

  29. Jefferson JW (1992) Is tranylcypromine really metabolized to amphetamine? J Clin Psychiat 53:450–451

    CAS  Google Scholar 

  30. Jones RS (1982) Tryptamine: a neuromodulator or neurotransmitter in mammalian brain? Prog Neurobiol 19:117–139

    Article  PubMed  CAS  Google Scholar 

  31. Kang GI, Chung SY (1984) Identification of N-acetyl and hydroxylated N-acetyltranylcypromine from tranylcypromine-dosed rat urine. Arch Pharm Res (Korea) 7:65–68

    Article  CAS  Google Scholar 

  32. Lerman C, Caporaso N, Main D, Audrain J, Boyd NR, Bowman ED, Shields PG (1998) Depression and self-medication with nicotine: the modifying influence of the dopamine D4 receptor gene. Health Psychol 17:56–62

    Article  PubMed  CAS  Google Scholar 

  33. Lloyd KG, Zivkovic B, Scatton B, Morselli PL, Bartholini G (1989) The gabaergic hypothesis of depression. Prog Neuropsychopharmacol Biol Psychiat 13:341–351

    Article  CAS  Google Scholar 

  34. Locock RA, Baker GB, Coutts RT, Dewhurst WG (1984) Displacement of serotonin from binding sites in rat cortex: the effects of biogenic “trace” amines. Prog Neuropsychopharmacol Biol Psychiat 8:701–704

    Article  CAS  Google Scholar 

  35. Lotufo-Neto F, Trivedi M, Thase ME (1999) Meta-analysis of the reversible inhibitors of monoamine oxidase type A moclobemide and brofaromine for the treatment of depression. Neuropsychopharmacology 20:226–247

    Article  PubMed  CAS  Google Scholar 

  36. Mallinger AG, Edwards DJ, Himmelhoch JM, Knopf S, Ehler J (1986) Pharmacokinetics of tranylcypromine in patients who are depressed: relationship to cardiovascular effects. Clin Pharmacol Ther 40:444–450

    Article  PubMed  CAS  Google Scholar 

  37. McManus DJ, Greenshaw AJ (1991) Differential effects of chronic antidepressants in behavioural tests of beta-adrenergic and GABAB receptor function. Psychopharmacology (Berl) 103:204–208

    Article  CAS  Google Scholar 

  38. McManus DJ, Mousseau DD, Paetsch PR, Wishart TB, Greenshaw AJ (1991) Beta-adrenoceptors and antidepressants: possible 2-phenylethylamine mediation of chronic phenelzine effects. Biol Psychiat 30:1122–1130

    Article  PubMed  CAS  Google Scholar 

  39. Mousseau DD, McManus DJ, Baker GB, Juorio AV, Dewhurst WG, Greenshaw AJ (1993) Effects of age and of chronic antidepressant treatment on [3H]tryptamine and [3H]dihydroalprenolol binding to rat cortical membranes. Cell Mol Neurobiol 13:3–13

    Article  PubMed  CAS  Google Scholar 

  40. Ordway GA, Gambarana C, Tejani-Butt SM, Areso P, Hauptmann M, Frazer A (1991) Preferential reduction of binding of 125I-iodopindolol to beta-1 adrenoceptors in the amygdala of rat after antidepressant treatments. J Pharmacol Exp Ther 257:681–690

    PubMed  CAS  Google Scholar 

  41. Paetsch PR, Greenshaw AJ (1992) Effects of chronic antidepressant treatment on dopamine-related [3H]SCH 23390 and [3H]spiperone binding in the rat striatum. Cell Mol Neurobiol 12:597–606

    Article  PubMed  CAS  Google Scholar 

  42. Parkington HC, Coleman HA, Tare M (2004) Prostacyclin and endothelium-dependent hyperpolarization. Pharmacol Res 49:509–514

    Article  PubMed  CAS  Google Scholar 

  43. Paterson IA, Boulton AA (1988) Beta-phenylethylamine enhances single cortical neurone responses to noradrenaline in the rat. Brain Res Bull 20:173–177

    Article  PubMed  Google Scholar 

  44. Raiteri M, Del Carmine R, Bertollini A, Levi G (1977) Effect of sympathomimetic amines on the synaptosomal transport of noradrenaline, dopamine and 5-hydroxytryptamine. Eur J Pharmacol 41:133–143

    Article  PubMed  CAS  Google Scholar 

  45. Rapoport SI, Bosetti F (2002) Do lithium and anticonvulsants target the brain arachidonic acid cascade in bipolar disorder? Arch Gen Psychiat 59:592–596

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  47. Riederer P, Lachenmayer L, Laux G (2004) Clinical applications of MAO-inhibitors. Curr Med Chem 11:2033–2043

    PubMed  CAS  Google Scholar 

  48. 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 24:63–76

    Article  PubMed  CAS  Google Scholar 

  49. Sands SA, Reisman SA, Enna SJ (2003) Effects of stress and tranylcypromine on amphetamine-induced locomotor activity and GABA(B) receptor function in rat brain. Life Sci 72:1085–1092

    Article  PubMed  CAS  Google Scholar 

  50. Sands SA, Reisman SA, Enna SJ (2004) Effect of antidepressants on GABA(B) receptor function and subunit expression in rat hippocampus. Biochem Pharmacol 68:1489–1495

    Article  PubMed  CAS  Google Scholar 

  51. Sherry RL, Rauw G, McKenna KF, Paetsch PR, Coutts RT, Baker GB (2000) Failure to detect amphetamine or 1-amino-3-phenylpropane in humans or rats receiving the MAO inhibitor tranylcypromine. J Affect Disord 61:23–29

    Article  PubMed  CAS  Google Scholar 

  52. Sherry-McKenna RL, Baker GB, Mousseau DD, Coutts RT, Dewhurst WG (1992) 4-Methoxytranylcypromine, a monoamine oxidase inhibitor: effects on biogenic amines in rat brain following chronic administration. Biol Psychiat 31:881–888

    PubMed  CAS  Google Scholar 

  53. Simopoulos AP (2002) Omega-3 fatty acids in inflammation and autoimmune diseases. J Am Coll Nutr 21:495–505

    PubMed  CAS  Google Scholar 

  54. Smith DF (1980) Tranylcypromine stereoisomers, monoaminergic neurotransmission and behavior. A minireview. Pharmakopsychiatr Neuropsychopharmakol 13:130–136

    PubMed  CAS  Google Scholar 

  55. Spahn-Langguth H, Hahn G, Mutschler E, Mohrke W, Langguth P (1992) Enantiospecific high-performance liquid chromatographic assay with fluorescence detection for the monoamine oxidase inhibitor tranylcypromine and its applicability in pharmacokinetic studies. J Chromatogr 584:229–237

    PubMed  CAS  Google Scholar 

  56. Taavitsainen P, Juvonen R, Pelkonen O (2001) In vitro inhibition of cytochrome P450 enzymes in human liver microsomes by a potent CYP2A6 inhibitor, trans-2-phenylcyclopropylamine (tranylcypromine), and its nonamine analog, cyclopropylbenzene. Drug Metab Dispos 29:217–222

    PubMed  CAS  Google Scholar 

  57. Thase ME, Trivedi MH, Rush AJ (1995) MAOIs in the contemporary treatment of depression. Neuropsychopharmacology 12:185–219

    Article  PubMed  CAS  Google Scholar 

  58. Tunnicliff G, Malatynska E (2003) Central GABAergic systems and depressive illness. Neurochem Res 28:965–976

    Article  PubMed  CAS  Google Scholar 

  59. Weber-Grandke H, Hahn G, Mutschler E, Mohrke W, Langguth P, Spahn-Langguth H (1993) The pharmacokinetics of tranylcypromine enantiomers in healthy subjects after oral administration of racemic drug and the single enantiomers. Br J Clin Pharmacol 36:363–365

    PubMed  CAS  Google Scholar 

  60. Weiser M, Reichenberg A, Grotto I, Yasvitzky R, Rabinowitz J, Lubin G, Nahon D, Knobler HY, Davidson M (2004) Higher rates of cigarette smoking in male adolescents before the onset of schizophrenia: a historical-prospective cohort study. Am J Psychiat 161:1219–1223

    Article  PubMed  Google Scholar 

  61. Winkler JD, Fonteh AN, Sung CM, Heravi JD, Nixon AB, Chabot-Fletcher M, Griswold D, Marshall LA, Chilton FH (1995) Effects of CoA-independent transacylase inhibitors on the production of lipid inflammatory mediators. J Pharmacol Exp Ther 274:1338–1347

    PubMed  CAS  Google Scholar 

  62. Youdim MB, Aronson JK, Blau K, Green AR, Grahame-Smith DG (1979) Tranylcypromine (‘Parnate’) overdose: measurement of tranylcypromine concentrations and MAO inhibitory activity and identification of amphetamines in plasma. Psychol Med 9:377–382

    Article  PubMed  CAS  Google Scholar 

  63. Yu PH (2001) Involvement of cerebrovascular semicarbazide-sensitive amine xidase in the pathogenesis of Alzheimer’s disease and vascular dementia. Med Hypotheses 57: 175–179

    Article  PubMed  CAS  Google Scholar 

  64. Zhang W, Kilicarslan T, Tyndale RF, Sellers EM (2001) Evaluation of methoxsalen, tranylcypromine, and tryptamine as specific and selective CYP2A6 inhibitors in vitro. Drug Metab Dispos 29:897–902

    PubMed  CAS  Google Scholar 

  65. Rössner A, Weber A, Becker A, Beck G, Kornhuber J, Frieling H, Bleich S (2006) Decreased serum semicarbazide sensitive aminooxidase (SSAO) activity in patients with major depression. Progress in Neuro-Psychopharmacology and Biological Psychiatry (In Press)

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  1. Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University of Erlangen-Nuremberg, Schwabachanlage 6, 91054, Erlangen, Germany

    Helge Frieling MD & Stefan Bleich MD

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Correspondence to Helge Frieling MD.

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Frieling, H., Bleich, S. Tranylcypromine. Eur Arch Psychiatry Clin Neurosci 256, 268–273 (2006). https://doi.org/10.1007/s00406-006-0660-8

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