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Brofaromine

Insight into the Nature of Drug Development

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Summary

Brofaromine is a reversible and selective inhibitor of monoamine oxidase type A. Available preclinical and clinical data indicate that brofaromine is an effective and well tolerated treatment for major depression and anxiety disorders. Despite these encouraging findings, the manufacturer (CIBA) terminated the development of this compound in 1993. The main reason for this termination has been problems with resources associated with the necessity to perform further placebo-controlled trials. The brofaromine story illustrates the complex, and often frustrating, nature of drug development.

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References

  1. Waldmeier PC, Felner AE, Tipton K. The monoamine oxidase inhibiting properties of CGP 11305 A. Eur J Pharmacol 1983; 94: 73–83

    Article  PubMed  CAS  Google Scholar 

  2. Waldmeier PC, Glatt A, Jaekel J, et al. Brofaromine: a monoamine oxidase-A and serotonin uptake inhibitor. Clin Neuropharmacol 1993; 16(2 Suppl.): S19–24

    PubMed  Google Scholar 

  3. Waldmeier PC, Baumann PA. Effects of CGP 11305 A: a new reversible and selective inhibitor of MAO A, on biogenic amine levels and metabolism in the rat brain. Naunyn Schmiedebergs Arch Pharmacol 1983; 324: 20–6

    Article  PubMed  CAS  Google Scholar 

  4. Waldmeier PC, Graf T, Germer M, et al. Serotonin uptake inhibition by the monoamine oxidase inhibitor brofaromine. Biol Psychiatry 1993; 33: 373–9

    Article  PubMed  CAS  Google Scholar 

  5. Waldmeier PC. Newer aspects of the reversible inhibitor of MAO-A and serotonin reuptake, brofaromine. Prog Neuropsychopharmacol Biol Psychiatry 1993; 17: 183–98

    Article  PubMed  CAS  Google Scholar 

  6. Gleiter CH, Nilsson E, Mühlbauer B, et al. Effect of the selective MAO-A inhibitors brofaromine, clorgyline and moclobemide on human platelet MAO-B activity. J Neural Transm Gen Sect 1992; 89: 129–33

    Article  PubMed  CAS  Google Scholar 

  7. Antonin KH, Kucher K, Fuchs L, et al. Investigation of dose proportionality and absolute bioavailability of brofaromine in healthy volunteers [abstract]. Clin Neuropharmacol 1992; 15Suppl. 1 (Pt. B): 430

    Article  Google Scholar 

  8. Antonin KH, Jedrychowski M, Bieck PR. Brofaromine: pharmacodynamic and pharmacokinetic investigations in healthy subjects with a new reversible, selective MAO-A inhibitor. Münch Med Wschr 1990; 132Suppl. 1: 13–7

    Google Scholar 

  9. Bieck PR, Schick C, Aichele G, et al. Oral tyramine pressor tests and tyramine kinetics in subjects treated with different MAO inhibitors. In: Shagass C, Josiassen RC, Bridger WH, et al., editors. Biological psychiatry. New York: Elsevier, 1985: 335–7

    Google Scholar 

  10. Bieck PR, Antonin K. Tyramine potentiation during treatment with MAO inhibitors: brofaromine and moclobemide vs irreversible inhibitors [abstract]. Psychopharmacology 1988; 96: 31

    Google Scholar 

  11. Bieck PR, Antonin KH. Oral tyramine pressor test and the safety of monoamine oxidase inhibitor drugs: comparison of brofaromine and tranylcypromine in healthy subjects. J Clin Psychopharmacol 1988; 8: 237–45

    Article  PubMed  CAS  Google Scholar 

  12. Bieck PR, Antonin KH. Tyramine potentiation during treatment with MAO inhibitors: brofaromine and moclobemide vs irreversible inhibitors. J Neural Transm Gen Sect 1989; Suppl. 28: 21–32

    Google Scholar 

  13. Gleiter CH, Mühlbauer B, Schulz RM, et al. Monoamine oxidase inhibition by MAO-A inhibitors brofaromine and clorgyline in healthy volunteers. J Neural Transm Gen Sect 1994; 95: 241–5

    Article  PubMed  CAS  Google Scholar 

  14. Delcker A, Gaertner HJ. Tolerability and antidepressive effect of brofaromine, a short acting reversible MAO-inhibitor - an open study. Eur Neuropsychopharmacol 1991; 1: 177–80

    Article  PubMed  CAS  Google Scholar 

  15. Hoencamp E, Haffmans PMJ, Knegtering H. Brofaromine in therapy resistant depression [abstract]. Biol Psychiatry 1991; 29: 374S–374SX

    Google Scholar 

  16. Jansen PAF, Haffmans PMJ. Evaluation of brofaromine in depressed elderly patients. Int Congress Symp Series 1992; 127: 27–30

    Google Scholar 

  17. Steiger A, Holsboer F, Gerken A, et al. Results of an open clinical trial of brofaromine (CGP 11 305 A), a competitive, selective, and short acting inhibitor of MAO-A in major endogenous depression. Pharmacopsychiatry 1987; 20: 262–9

    Article  PubMed  CAS  Google Scholar 

  18. Steiger A, Bardeleben U von, Guldner J, et al. The sleep, EEG and nocturnal hormonal secretion studies on changes during the course of depression and on effects of CNS-active drugs. Prog Neuropsychopharmacol Biol Psychiatry 1993; 17: 125–37

    Article  PubMed  CAS  Google Scholar 

  19. Schiwy W, Heath WR, Delini-Stula A. Therapeutic and side-effect profile of a selective and reversible MAO-A inhibitor, brofaromine: results of dose-finding trials in depressed patients. J Neural Transm Gen Sect 1989; Suppl. 29: 33–44

    Google Scholar 

  20. Volz HP, Heimann H, Bellaire J, et al. Brofaromine in non-endogenous major depressed inpatients: results of a preliminary dose-finding trial versus tranylcypromine. Pharmacopsychiatry. In press

  21. Möller HJ, Volz HP. Brofaromine in elderly major depressed patients - a comparative trial versus imipramine. Eur Neuropsychopharmacol 1993; 3: 501–10

    Article  PubMed  Google Scholar 

  22. Volz HP, Möller HJ. Brofaromine in major depressed in-patients: a controlled clinical trial versus imipramine. Eur Neuropsychopharmacol 1994; 27: 152–8

    CAS  Google Scholar 

  23. Möller HJ, Volz HP. Brofaromine in major depressed patients: a controlled clinical trial versus imipramine and open follow-up of up to one year. J Affect Disord 1992; 26: 163–72

    Article  PubMed  Google Scholar 

  24. Volz HP, Faltus F, Magyar I, et al. Brofaromine in treatment resistant major depressed patients - a comparative trial versus tranylcypromine. J Affect Disord 1994; 30: 209–17

    Article  PubMed  CAS  Google Scholar 

  25. Nolen WA, Haffmans PMJ, Bouvy PF, et al. Monoamine oxidase inhibitors in resistant major depression. A double-blind comparison of brofaromine and tranylcypromine in patients resistant to tricyclic antidepressants. J Affect Disord 1993; 28: 189–97

    Article  PubMed  CAS  Google Scholar 

  26. Chouinard G, Saxena BM, Nair NPV, et al. A Canadian multicentre placebo-controlled study of a fixed dose of brofaromine, a reversible selective MAO-A inhibitor, in the treatment of major depression. J Affect Disord. In press

  27. Van Vliet IM, Westenberg HGM, Den Boer JA. MAO inhibitors in panic disorder. Clinical effects of treatment with brofaromine: a double blind placebo controlled study. Psychopharmacology 1993; 112: 483–9

    Article  PubMed  Google Scholar 

  28. Van Vliet IM, Westenberg HGM, Den Boer JA. The efficacy of a reversible MAO inhibitor, brofaromine, in social phobia [abstract]. Biol Psychiatry 1991; 29: 372S–372SX

    Google Scholar 

  29. Van Vliet IM, Den Boer JA, Westenberg HG. Psychopharmacological treatment of social phobia: clinical and biochemical effects of brofaromine, a selective MAO-A inhibitor. Eur Neuropsychopharmacol 1992; 2: 21–9

    Article  PubMed  Google Scholar 

  30. Struck M, Venable N, Snaith J. Brofaromine in the treatment of panic disorder. Fortschr Neurol Psychiatr 1994; 61(1 Sonderheft): 27

    Google Scholar 

  31. Den Boer JA, Van Vliet IM, Westenberg HGM. A double blind comparative study of fluvoxamine and brofaromine in panic disorder [abstract]. Clin Neuropharmacol 1992; 15: 91B–91BX

    Article  Google Scholar 

  32. Bakish D, Saxena BM, Bowen R, et al. Reversible monoamine oxidase-A inhibitors in panic disorder. Clin Neuropharmacol 1993; 16Suppl. 2: S77–82

    PubMed  Google Scholar 

  33. Garcia-Borreguerro D, Bronisch T. Improvement of social phobic symptoms after treatment with brofaromine, a reversible and selective inhibitor of MAO-A. Eur Psychiatry 1992; 7: 93–4

    Google Scholar 

  34. Den Boer JM, van Vliet IM, Westenberg HGM. A double-blind comparative study of fluvoxamine and brofaromine in panic disorder [abstract]. Clin Neuropharmacol 1992; 15(1 Suppl. B): 9

    Google Scholar 

  35. Fahlén T, Humble M, Koczkas C, et al. Social phobia and its treatment with brofaromine, efficacy regarding social phobia symptoms and personality traits [abstract]. Clin Neuropharmacol 1992; 15: 64B–64BX

    Article  Google Scholar 

  36. Garcia-Borreguerro D, Lauer CJ, Özdaglar A, et al. Brofaromine in panic disorder: a pilot study with a new reversible inhibitor of monoamine oxidase-A. Pharmacopsychiatry 1992; 25: 261–4

    Article  Google Scholar 

  37. Kennedy SH, Goldbloom DS, Ralevski E, et al. Is there a role for selective monoamine oxidase inhibitor therapy in bulimia nervosa? A placebo-controlled trial of brofaromine. J Clin Psychopharmacol 1993; 13: 415–22

    Article  PubMed  CAS  Google Scholar 

  38. Hohagen F, Mayer G, Riemann D, et al. Treatment of narcolepsy-cataplexy-syndrome with the new selective and reversible MAO-A inhibitor brofaromine - a pilot study. Biol Psychiatry 1991; 28: 305S–305SX

    Google Scholar 

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Authors and Affiliations

  1. Psychiatric Department of the University of Jena, Philosophenweg 3, D-07740, Jena, Germany

    Hans-Peter Volz

  2. Department of Clinical Pharmacology, University of Göttingen, Göttingen, Germany

    Christoph H. Gleiter

  3. CIBA Limited, European Clinical Research and Development CNS, Basle, Switzerland

    Michael Struck

  4. Psychiatric Department of the University of Bonn, Bonn, Germany

    Hans-Jürgen Möller

Authors
  1. Hans-Peter Volz
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  2. Christoph H. Gleiter
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  3. Michael Struck
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  4. Hans-Jürgen Möller
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Volz, HP., Gleiter, C.H., Struck, M. et al. Brofaromine. CNS Drugs 3, 1–8 (1995). https://doi.org/10.2165/00023210-199503010-00001

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