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Clinical Pharmacokinetics of the Monoamine Oxidase-A Inhibitor Moclobemide

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  • Drug Disposition
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Summary

There has been a resurgence of interest in the use of monoamine oxidase (MAO) enzyme inhibitors for the treatment of depression. Unlike the first-generation MAO inhibitors, the current drugs are readily reversible in their action, resulting in far less concern about interactions with certain foods and drugs which could lead to serious pressor effects. Furthermore, the current drugs are far more selective in their actions as a result of the ability to affect either the MAO-A or the MAO-B isoenzyme. Moclobemide is an example of a reversible MAO-A inhibitor which has been extensively studied and whose pharmacokinetic, clinical pharmacological and toxicological profiles have been thoroughly defined.

Moclobemide has a short disposition half-life and intermediate values for systemic clearance and volume of distribution; half-life increases somewhat with dose. The drug is completely metabolised by the liver. Moclobemide is rapidly and completely absorbed following oral administration in a variety of dosages and forms. The drug has a high intrinsic (apparent oral) clearance which results in a substantial hepatic first-pass effect and, while there is marked interindividual variation, differences within an individual are small. A time- and dose-dependence is observed with multiple oral administration: clearance decreases with administration during the first week and thereafter remains constant. The exact mechanism of this effect is not known, but it may reflect inhibition of elimination by metabolites (the kinetics may always be described as being first-order).

Moclobemide disposition is not affected by renal disease, nor is there substantial alteration with advanced age. Liver disease causes a dramatic reduction in clearance; dosage must be adjusted for patients with liver disease. There is minimal transfer of the drug into breast milk, such that breast-feeding neonates are exposed to only a very small dose of the drug.

Moclobemide administration results in a minimal interaction with exogenous amines (e.g. tyramine and pressor amine drugs); the so-called ‘cheese effect’ is therefore of little concern. As a result, the drug has an excellent tolerability profile both within the therapeutic dose range and in overdose (no deaths have been attributed to moclobemide intoxication per se). Cimetidine inhibits the elimination of moclobemide. Moclobemide appears to affect several isoenzymes of the cytochrome P450 (CYP) system (CYP2C19, CYP2D6 and CYP1A2). The adverse events profile of moclobemide indicates only mild and transient effects at a relatively low rate of occurrence.

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References

  1. Bloch RG, Dooneief AS, Buchberg AS, et al. The clinical effect of isoniazid and iproniazid in the treatment of pulmonary tuberculosis. Ann Intern Med 1954; 40: 881–900

    PubMed  CAS  Google Scholar 

  2. Crane GE. Further studies on iproniazid phosphate. J Nerv Mental Dis 1956; 124: 322–31

    CAS  Google Scholar 

  3. Kline NS. Clinical experiences with iproniazid (Marsilid). J Clin Psychopathol 1958; 19 Suppl.: 78–9

    Google Scholar 

  4. Rigal F, Zarifian E. MAO inhibitors in psychiatric therapy: effects and side effects. Modern Problems Pharmacopsychiatr 1983; 19: 162–9

    CAS  Google Scholar 

  5. Blackwell B. Hypertensive crisis due to monoamine-oxidase inhibition. Lancet 1963; ii: 849–51

    Google Scholar 

  6. Nies A. Differential response patterns to MAO inhibitors and tricyclics. J Clin Psychiat 1984; 45: 70–7

    CAS  Google Scholar 

  7. Johnston JP. Some observations upon a new inhibitor of monoamine oxidase in human brain. Biochem Pharmacol 1968; 17: 1285–97

    PubMed  CAS  Google Scholar 

  8. Brunner HG, Nelen MR, van Zandvoort P, et al. X-linked borderline mental retardation with prominent behavioral disturbance: phenotype, genetic localization, and evidence for disturbed monoamine metabolism. Am J Human Genet 1993; 52: 1032–9

    CAS  Google Scholar 

  9. Morell V. Evidence found for a possible ‘aggression gene’. Science 1993; 260: 1722–3

    PubMed  CAS  Google Scholar 

  10. Dostert PL, Benedetti MS, Tipton KF. Interactions of monoamine oxidase with substrates and inhibitors. Med Res Rev 1989; 9: 45–89

    PubMed  CAS  Google Scholar 

  11. Benedetti MS, Dostert P. Monoamine oxidase: from physiology and pathophysiology to the design and clinical application of reversible inhibitors. Adv Drug Res 1992; 23: 67–125

    Google Scholar 

  12. Cesura AM, Pletscher A. The new generation of monoamine oxidase inhibitors. Progr Drug Res 1992; 38: 174–297

    Google Scholar 

  13. Tipton KF, O’Carroll AM, McCrodden JM. The catalytic behaviour of monoamine oxidase. J Neural Transmission 1987; 23 Suppl.: 23–35

    Google Scholar 

  14. Denney RM, Denney CB. An uptake on the identity crisis of monoamine oxidase: new and old evidence for the independence of MAOA and B. Pharmacol Ther 1985; 30: 227–59

    PubMed  CAS  Google Scholar 

  15. Weyler W, Hsu YP, Breakefield XO. Biochemistry and genetics of monoamine oxidase. Pharmacol Ther 1990; 47: 391–417

    PubMed  CAS  Google Scholar 

  16. Zhu Q, Grimsby J, Chen K, et al. Promoter organization and activity of human monoamine oxidase (MAO) A and B genes. J Neurosci 1992: 12: 4437–46

    PubMed  CAS  Google Scholar 

  17. Kochersperger LM, Parker EL, Siciliano M, et al. Assignment of genes for human monoamine oxidase A and B to the X chromosome. J Neurosci Res 1986; 16: 602–16

    Google Scholar 

  18. Saura J, Kettler R, Da Prada M, et al. Quantitative enzyme radioautography with 3H-Ro 41-1049 and 3H-Ro 19-6327 in vitro: localization and abundance of MAO-A and MAO-B in rat CNS, peripheral organs, and human brain. J Neurosci 1992; 12: 1977–99

    PubMed  CAS  Google Scholar 

  19. Youdim MBH, Finberg JPM. New directions in monoamine oxidase A and B: selective inhibitors and substrates. Biochem Pharmacol 1990; 41: 155–62

    Google Scholar 

  20. Nakamura S, Kawamata T, Akiguchi I, et al. Expression of monoamine oxidase B activity in astrocytes of senile plaques. Acta Neuropathol 1990; 80: 319–25

    Google Scholar 

  21. Calne DB. The free radical hypothesis in Parkinsons’s disease: evidence supporting it. Ann Neurol 1992; 32: 804–12

    Google Scholar 

  22. Cohen G. Monoamine oxidase, hydrogen peroxide and Parkinson’s disease. Adv Neurol 1986; 45: 119–29

    Google Scholar 

  23. Fahn S, Cohen G. The oxidant stress hypothesis in Parkinson’s disease: evidence supporting it. Ann Neurol 1992; 32: 804–12

    PubMed  CAS  Google Scholar 

  24. Strolin-Benedetti M, Dostert P. Monoamine oxidase, brain ageing and degenerative diseases. Biochem Pharmacol 1989; 38: 555–61

    PubMed  CAS  Google Scholar 

  25. Zhu Q, Grimsby J, Chen K, et al. Promoter organization and activity of human monoamine oxidase (MAO) A and B genes. J Neurosci 1992; 12: 4437–46

    PubMed  CAS  Google Scholar 

  26. Arnett CD, Fowler JS, MacGregor RR, et al. Turnover of brain monoamine oxidase in vivo by positron emission tomography using L-[11C]deprenyl. J Neurochem 1987; 49: 522–27

    PubMed  CAS  Google Scholar 

  27. Oreland L, Jossan SS, Hartvig P, et al. Turnover of monoamine oxidase B (MAO-B) in pig brain by positron emission tomography using 11-L-deprenyl. J Neural Transm Suppl 1990; 32: 55–9

    PubMed  CAS  Google Scholar 

  28. Guentert TW, Mayersohn M. Clinical-pharmacokinetic profile of moclobemide and its comparison with other MAO-inhibitors. Rev Contemp Pharmacother 1994; 5: 19–34

    Google Scholar 

  29. Geschke R, Koerner J, Eggers H. Determination of the new monoamine oxidase inhibitor moclobemide and three of its metabolites in biological fluids by high-performance liquid chromatography. J Chromatogr 1987; 420: 111–20

    PubMed  CAS  Google Scholar 

  30. Raaflaub J, Haefelfinger P, Trautmann KH. Single-dose pharmacokinetics of the MAO-inhibitor moclobemide in man. Arzneimittelforschung 1984; 34: 80–2

    PubMed  CAS  Google Scholar 

  31. Schoerlin MP, Mayersohn M, Hoevels B, et al. Cimetidine alters the disposition kinetics of the monoamine oxidase-A inhibitor moclobemide. Clin Pharmacol Ther 1991; 49: 32–8

    PubMed  CAS  Google Scholar 

  32. Schoerlin MP, Korn A, Zeller M, et al. Bioavailability of moclobemide from the controlled-release tablets /015 and /019 relative to intravenous and oral solutions. Data on file, F. Hoffmann-LaRoche Ltd, Basel, 1986

    Google Scholar 

  33. Schoerlin MP, Mayersohn M, Korn A, et al. Disposition kinetics of moclobemide, a monoamine oxidase-A enzyme inhibitor: single and multiple dosing in normal subjects. Clin Pharmacol Ther 1987; 42: 395–404

    PubMed  CAS  Google Scholar 

  34. Guentert TW, Waldburger R, Stebler T, et al. Bioavailability of moclobemide after a 200-mg tablet formulation (Ro 11-1163/035) in comparison to the 150-mg tablet (Ro 11-1163/026) and the intravenous dosage form (Ro 11-1163/004) and multiple dose kinetics following 200 mg b.i.d. Data on file, F. Hoffmann-LaRoche Ltd, Basel, 1992

    Google Scholar 

  35. Birnboeck H, Bock J, Bryant M, et al. Absolute bioavailability and multiple-dose kinetics of moclobemide after a new tablet formulation (300 mg; Ro 11-1163/057) in comparison with the 150 mg tablet Ro 11-1163/026. Data on file, F. Hoffmann-LaRoche Ltd, Basel, 1993

    Google Scholar 

  36. Tucker G, Guentert TW, Haefelfinger P, et al. Single dose and multiple dose pharmacokinetics of moclobemide after administration of the commercial 150-mg tablet (/026). Data on file, F. Hoffmann-LaRoche Ltd, Basel, 1988

    Google Scholar 

  37. Meyer J, Brandt R. Plasma protein binding of Ro 11-1163 in dog and man. Data on file, F. Hoffmann-LaRoche Ltd, Basel, 1983

    Google Scholar 

  38. Schoerlin MP, Guentert T, Raaflaub, et al. Plasma level monitoring and passage of Ro 11-1163 into cerebrospinal fluid during a 4-week efficacy study with multiple oral doses of the monoamine oxidase inhibitor Ro 11-1163 to six patients. Data on file, F. Hoffmann-LaRoche Ltd, Basel, 1984

    Google Scholar 

  39. Lam FC, Hung CT, Perrier DG. Estimation of variance for harmonic mean half-lives. J Pharm Sci 1985; 74: 229–31

    PubMed  CAS  Google Scholar 

  40. Mayersohn M, Hamilton R. Relationship between the terminal disposition half-life and mean residence time in multicompartment models. Drug Metab Dispos 1993; 21: 1172–3

    PubMed  CAS  Google Scholar 

  41. Wiesel F-A, Raaflaub J, Kettler R. Pharmacokinetics of oral moclobemide in healthy human subjects and effects on MAO-activity in platelets and excretion of urine monoamine metabolites. Eur J Clin Pharmacol 1985; 28: 89–95

    PubMed  CAS  Google Scholar 

  42. Tahara H, Shimokawa M, Kuruma I. A pharmacokinetic study of single- and multiple-oral dosing of moclobemide (Ro 11-1163) to normal healthy volunteers. Data on file, F. Hoffmann-LaRoche Ltd, Basel, 1990

    Google Scholar 

  43. Schoerlin MP, Mayersohn M, Hoevels B, et al. Effect of food intake on the relative bioavailability of moclobemide (Ro 11-1163). Data on file, F. Hoffmann-LaRoche Ltd, Basel, 1987

    Google Scholar 

  44. Mayersohn M, Schoerlin MP, Korn A, et al. Relative oral bioavailability of moclobemide from solution, tablet and capsule formulations. Data on file, F. Hoffmann-LaRoche Ltd, Basel, 1986

    Google Scholar 

  45. Schoerlin MP, Saletu B, Vranesic D, et al. Plasma concentrations after different single oral doses (100, 200 and 400 mg) of moclobemide (Ro 11-1163) in healthy volunteers. Data on file, F. Hoffmann-LaRoche Ltd, 1986

  46. Schoerlin MP, Eggers H, Peuckert V, et al. Pharmacokinetics of moclobemide (Ro 11-1163) in a tolerability study with ascending single oral doses in healthy male volunteers. Data on file, F. Hoffmann-LaRoche Ltd, 1987

  47. Williams PEO, Muirhead GJ, James AG. Moclobemide pharmacokinetics after single oral doses of 150 mg in young male volunteers. Data on file, F. Hoffmann-LaRoche Ltd, 1986

  48. Wilkinson GR, Shand DG. A physiological approach to hepatic drug clearance. Clin Pharmacol Ther 1975; 18: 377–90

    PubMed  CAS  Google Scholar 

  49. Jauch R, Griesser E, Oesterhelt G, et al. Biotransformation of moclobemide in humans. Acta Psychiatr Scand 1990; 82 Suppl. 360: 87–90

    Google Scholar 

  50. Schoerlin MP, Blouin RA, Pfefen JP, et al. Comparison of the pharmacokinetics of moclobemide in poor and efficient metabolizers of debrisoquine. Acta Psychiatr Scand 1990; 82 Suppl. 360; 98–100

    Google Scholar 

  51. Schoerlin MP, Horber FF, Frey FJ, et al. Disposition kinetics of moclobemide, a new MAO-A inhibitor, in subjects with impaired renal function. J Clin Pharmacol 1990; 30: 272–84

    PubMed  CAS  Google Scholar 

  52. Stoeckel K, Pfefen JP, Mayersohn M, et al. Absorption and disposition of moclobemide in patients with advanced age or reduced liver or kidney function. Acta Psychiatr Scand 1990; 82 Suppl. 360: 94–7

    Google Scholar 

  53. Schoerlin MP, Mayersohn M, Hoffmann K, et al. Pharmacokinetics of moclobemide (Ro 11-1163) in patients with liver cirrhosis. Data on file, F. Hoffmann-LaRoche Ltd, Basel, 1987

    Google Scholar 

  54. Branch RA, James JA, Read AE. The clearance of antipyrine and indocyanine green in normal subjects and inpatients with chronic liver disease. Clin Pharmacol Ther 1976; 20: 81–9

    PubMed  CAS  Google Scholar 

  55. McLean A, du Souich P, Gibaldi M. Noninvasive kinetic approach to the estimation of total hepatic blood flow and shuntng in chronic liver disease — a hypothesis. Clin Pharmacol Ther 1979; 25: 161–6

    PubMed  CAS  Google Scholar 

  56. Mayersohn M. Special pharmacokinetic considerations in the elderly. In: Evans WE, Schentag JJ, Jusko WJ, editors. Applied pharmacokinetics. 2nd ed. Spokane, Washington: Applied Theraputics Inc., 1986; 229–93

    Google Scholar 

  57. Mayersohn M, Schoerlin MP, Dellenbach M, et al. Moclobemide absorption and disposition in healthy young and elderly subjects following single intravenous and oral dosing and multiple oral dosing. Data on file, F. Hoffmann-LaRoche Ltd, Basel, 1987

    Google Scholar 

  58. Maguire K, Pereira A, Tiller J. Moclobemide pharmacokinetics in depressed patients: lack of age effect. Hum Psychopharmacol 1991; 6: 249–52

    Google Scholar 

  59. Pons G, Schoerlin MP, Tarn YK, et al. Moclobemide excretion in human breast milk. Br J Clin Pharmacol 1990; 29: 27–31

    PubMed  CAS  Google Scholar 

  60. Schoerlin MP, Mayersohn M, Hoevels B, et al. Effect of food intake on the relative bioavailability of moclobemide (Ro 11-1163). J Neural Transm 1988; 26: 115–21

    CAS  Google Scholar 

  61. Cole AFD, Baxter JG, Jackson BJ, et al. Pharmacokinetic and metabolic aspects of the moclobemide-food interaction. Psychopharmacol 1992; 106 Suppl.: S37–S39

    CAS  Google Scholar 

  62. Blackwell B. Monoamine oxidase inhibitor interactions with other drugs. J Clin Psychopharmacol 1991; 11: 55–9

    PubMed  CAS  Google Scholar 

  63. Blackwell B, Marley E, Price J, et al. Hypertensive interactions between monoamine oxidase inhibitors and foodstuffs. Br J Psychiatry 1967; 113: 349–65

    PubMed  CAS  Google Scholar 

  64. Harrison WM, McGrath PJ, Stewart JW, et al. MAOIs and hypertensive crises: the role of OTC drugs. J Clin Psychiatr 1989; 50: 64–5

    CAS  Google Scholar 

  65. Hirsch MS, Walter RM, Hauterlik RJ. Subarachnoid hemorrhage following ephedrine and MAO inhibitor. JAMA 1965; 194: 1259

    PubMed  CAS  Google Scholar 

  66. Hunter KR, Boakes AJ, Laurence DR, et al. Monoamine oxidase inhibitor and L-dopa. BMJ 1970; 3: 388

    PubMed  CAS  Google Scholar 

  67. Teychenne PF, Calne DB, Lewis PJ, et al. Interactions of levodopa with inhibitors of monoamine oxidase and L-aromatic amino acid decarboxylase. Clin Pharmacol Ther 1975; 18: 273–7

    PubMed  CAS  Google Scholar 

  68. Da Prada M, Zuercher G, Wuethrich I, et al. On tyramine, food, beverages and the reversible MAO inhibitor moclobemide. J Neural Transm 1988; 26 Suppl.: 31–56

    Google Scholar 

  69. Browne B, Linter S. Monoamine oxidase inhibitors and narcotic analgesics — a critical review of the implications for treatment. Br J Psychiatry 1987; 151: 210–2

    PubMed  CAS  Google Scholar 

  70. Ciraulo DA, Shader RI. Fluoxetine drug-drug interactions, I: Antidepressants and antipsychotics. J Clin Psychopharmacol 1990; 10: 48–50

    PubMed  CAS  Google Scholar 

  71. Da Prada M, Kettler R, Keller HH, et al. Neurochemical profile of moclobemide, a short-acting and reversible inhibitor of monoamine oxidase type A. J Pharmacol Exp Ther 1989; 248: 400–14

    PubMed  Google Scholar 

  72. Korn A, Eichler HG, Fischbach R, et al. Moclobemide, a new reversible MAO inhibitor-interaction with tyramine and tricyclic antidepressants in healthy volunteers and depressive patients. Psychopharmacol 1986; 88: 153–7

    CAS  Google Scholar 

  73. Birnboeck H, Bork J, Bryant M, et al. Safety, tolerability and potential pharmacodynamic/pharmacokinetic interactions of combined moclobemide and clomipramine in healthy young volunteers. Data on file, Hoffmann-La Roche Ltd, 1993

  74. Dingemanse J, Kneer J, Fotteler B, et al. Switch in treatment from tricyclic antidepressants to moclobemide: a new generation monoamine oxidase inhibitor. J Clin Psychopharmacol 1995; 15: 41–8

    PubMed  CAS  Google Scholar 

  75. Zimmer R, Gieschke R, Fischbach R et al. Interaction studies with moclobemide. Acta Psychiatr Scand 1990; 82 Suppl. 360: 84–6

    Google Scholar 

  76. Dingemanse J. An update of recent moclobemide interaction data. Int Clin Psychopharmacol 1993; 7: 167–80

    PubMed  CAS  Google Scholar 

  77. Guentert TW, Schmitt M, Dingemanse J, et al. Influence of moclobemide on ibuprofen-induced faecal blood loss. Psychopharmacol 1992; 106 (Suppl.): S40–2

    CAS  Google Scholar 

  78. Amrein R, Guentert TW, Dingemanse J, et al. Interactions of moclobemide with concomitantly administered medication: evidence from pharmacological and clinical studies. Psychopharmacol 1992; 106 (Suppl.): S24–31

    CAS  Google Scholar 

  79. Wijnands S, Chang PC, Blauw GJ, et al. Potentiation of the pressor effect of oral and intravenous tyramine during administration of the selective MAO-A inhibitor moclobemide in healthy volunteers. J Psychopharmacol 1989; 3: 36–44

    PubMed  CAS  Google Scholar 

  80. Berlin I, Zimmer R, Cournot A, et al. Determination and comparison of the pressor effect of tyramine during long-term moclobemide and tranylcypromine treatment in healthy volunteers. Clin Pharmacol Ther 1989; 46: 344–51

    PubMed  CAS  Google Scholar 

  81. Korn A, Da Prada M, Raffesberg W, et al. Effect of moclobemide, a new reversible monoamine oxidase inhibitor, on absorption and pressor effect of tyramine. J Cardiovasc Pharmacol 1988; 11: 17–23

    PubMed  CAS  Google Scholar 

  82. Simpson GM, Gratz SS. Comparison of the pressor effect of tyramine after treatment with phenelzine and moclobemide in healthy male volunteers. Clin Pharmacol Ther 1992; 52: 286–91

    PubMed  CAS  Google Scholar 

  83. Gieschke R, Schmidt-Burgk W, Amrein R. Interaction of moclobemide, a new reversible monoamine oxidase inhibitor, and oral tyramine. J Neural Transm 1988; 26 Suppl.: 97–104

    CAS  Google Scholar 

  84. The cheese effect and new reversible MAO-A inhibitors. In: Youdim MBH, Da Prada M, Amrein R, editors. Proceedings of the Round Table of the International Conference on New Directions in Affective Disorders. 1987 Apr 5–9: Jerusalem. J Neural Transm 1988; 26 Suppl.: 1–136

  85. Da Prada M, Zuercher G. Tyramine content of preserved and fermented foods or condiments of Far Eastern cuisine. Psychopharmacol 1992; 106 Suppl.: S32–4

    Google Scholar 

  86. Bieck PR, Antonin KH, Schmidt E. Clinical pharmacology of reversible MAO-A inhibitors. Clin Neuropharmacol 1992; 15 Suppl. 1: 345A–346A

    PubMed  Google Scholar 

  87. Cesura AM, Kettler R, Da Prada M. Moclobemide, an established RIMA antidepressant: in vitro interactions with tyramine. In: G. Racagni, N. Brunello, T. Fukuda, editors. Biological psychiatry. Vol. 2. Proceedings of the 5th World Congress of Biological Psychiatry; 1991 Jun 9–14: Florence. Amsterdam: Elsevier Science, 1991; 843–5

    Google Scholar 

  88. Neuvonen PJ, Pohjola-Sintonen S, Vuori E. Five fatal cases of serotonin syndrome after moclobemide-citalopram or moclobemide-clomipramine overdoses. Lancet 1993; 342: 1419

    PubMed  CAS  Google Scholar 

  89. Brodribb TR, Downey M, Gilbar PJ. Efficacy and adverse effects of moclobemide. Lancet 1994; 343: 475

    PubMed  CAS  Google Scholar 

  90. Freeman J. Moclobemide — a reply. Lancet 1994; 343: 680

    Google Scholar 

  91. Elis J, Laurence DR, Mattie H, et al. Modification by monoamine oxidase inhibitors of the effect of some sympathomimetics on blood pressure. BMJ 1967; 2: 75–8

    PubMed  CAS  Google Scholar 

  92. Dingemanse J, Guentert TW, Moritz E, et al. Pharmacodynamic and pharmacokinetic interactions between fluoxetine and moclobemide. Clin Pharmacol Ther 1993; 53: 178

    Google Scholar 

  93. Graham PM, Potter JM, Paterson JW. Combination monoamine oxidase inhibitor/tricyclic antidepressant interaction. Lancet ii: 1982; 440

    Google Scholar 

  94. Von Oefele K, Grohmann R, Ruether E. Adverse drug reactions in combined tricyclic and MAOI therapy. Pharmacopsychiatry 1986; 19: 243–4

    Google Scholar 

  95. Von Oefele K, Grohmann R, Hippius H, et al. Unerwünschte Arzneimittelwirkungen bei der Kombinationsbehandlung mit trizyklischen Antidepressiva und Monoaminoxidase-Hemmern. Nervenarzt 1988; 59: 118–23

    Google Scholar 

  96. Cummings JL. Depression and Parkinson’s disease: a review. Am J Psychiatr 1992; 149: 443–54

    PubMed  CAS  Google Scholar 

  97. Pare CMB. The present status of monoamine oxidase inhibitors. Br J Psychiatr 1985; 146: 567–84

    Google Scholar 

  98. Horwitz D, Fox SM, Goldberg LI. Effects of dopamine in man. Circulat Res 1962; 10: 237–43

    PubMed  CAS  Google Scholar 

  99. Heinonen EH, Lammintausta R. A review of the pharmacology of selegiline. Acta Neurologica Scand 1991; 84 Suppl. 136: 44–59

    Google Scholar 

  100. Schulz R, Antonin KH, Hoffmann E, et al. Tyramine kinetics and pressor sensitivity during monoamine oxidase inhibition by selegiline. Clin Pharmacol Ther 1989; 46: 528–36

    PubMed  CAS  Google Scholar 

  101. Korn A, Dingemanse J, Da Prada M, et al. Tolerability and pharmacodynamic interactions of combined MAO-A and MAO-B inhibition by moclobemide and selegiline (with and without levodopa) in healthy man. Proceedings of the Vth World Conference of Clinical Pharmacology and Therapeutics; 1992 Jul 16–31: Yokohama, Japan

  102. Bélanger PM, Atitse-Gbeassor A. Inhibitory effect of tranylcypromine on hepatic drug metabolism in the rat. Biochem Pharmacol 1982; 31: 2679–83

    PubMed  Google Scholar 

  103. Dupont H, Davies DS, Strolin-Benedetti M. Inhibition of cytochrome P-450-dependent oxidation reactions by MAO inhibitors in rat liver microsomes. Biochem Pharmacol 1987; 36: 1651–7

    PubMed  CAS  Google Scholar 

  104. Jonen HG, Werringloer J, Prough RA, et al. The reaction of phenylhydrazine with microsomal cytochrome P-450. J Biol Chem 1982; 257: 4404–11

    PubMed  CAS  Google Scholar 

  105. Moloney SJ, Snider BJ, Prough RA. The interactions of hydrazine derivatives with rat-hepatic cytochrome P-450. Xenobiotica 1984; 14: 803–14

    PubMed  CAS  Google Scholar 

  106. Callingham BA, Valoti M, Sgaragli P. Drug and enzyme interactions with moclobemide. In: G. Racagni, N. Brunello, T. Fukuda, editors. Biological psychiatry. Vol. 2. Proceedings of the 5th World Congress of Biological Psychiatry; 1991 Jun 9–14: Florence. Amsterdam: Elsevier Science, 1991; 846–9

    Google Scholar 

  107. Rendic S, Kajfez F, Ruf HH. Characterization of cimetidine, ranitidine, and related structures interaction with cytochrome P-450. Drug Metab Dispos 1983; 11: 137–42

    PubMed  CAS  Google Scholar 

  108. Gram LF, Brøsen K. Moclobemide treatment causes a substantial rise in the sparteine metabolic ratio. Br J Clin Pharmacol 1993; 35: 649–52

    PubMed  CAS  Google Scholar 

  109. Dhadyalla AS, Lennard MS, Tucker GT, et al. In vitro inhibition of sparteine oxidation by moclobemide. Data on file, F. Hoffmann-La Roche Ltd, Basel, 1991

    Google Scholar 

  110. Crewe HK, Lennard MS, Tucker GT, et al. The effect of paroxetine and other specific 5-HT re-uptake inhibitors of cytochrome P450IID6 activity in human liver microsomes. Br J Clin Pharmacol 1991; 32: 658P–659P

    Google Scholar 

  111. Guentert TW, Grange S, Bock J, et al. Lack of an important influence of CYP2D6 oxidation status on the pharmacokinetics of moclobemide. Clin Pharmacol Ther 1995; 57: 151

    Google Scholar 

  112. Schoerlin MP, Blouin RA, Pfefen JP, et al. Comparison of pharmacokinetics of moclobemide in poor and efficient metabolizers of debrisoquine. Acta Psychiatr Scand 1990; 82 Suppl. 360; 98–100

    Google Scholar 

  113. Pfefen JP, Guentert TW, Blouin RA, et al. Comparison of pharmacokinetics of moclobemide in poor and extensive metabolizers of debrisoquine and mephenytoin: a retrospective analysis. Data on file, F. Hoffmann-La Roche Ltd, Basel, 1988

    Google Scholar 

  114. Guentert TW, Gram LF, Grange S, Brosen K. Reversible interaction of moclobemide with CYP2D6 and CYP2C9. Clin Pharmacol Ther 1994; 55: 137

    Google Scholar 

  115. Green AR, Grahame-Smith DG. Processes regulating the functional activity of brain 5-hydroxytryptamine: results of animal experimentation and their relevance to the understanding and treatment of depression. Pharmakopsychiatrie 1978; 11: 3–16

    Google Scholar 

  116. Waldmeier PC. Amine oxidases and their endogenous substrates. J Neural Transm 1987; 23 Suppl.: 55–72

    CAS  Google Scholar 

  117. Scheinin M, Karhuvaara S, Ojala-Karlsson P, et al. Plasma 3,4-dihydroxyphenylglycol (DHPG) and 3-methoxy-4-hydroxyphenylglycol (MHPG) are insensitive indicators of a2-adrenoceptor mediated regulation of norepinephrine release in healthy human volunteers. Life Sci 1991; 49: 75–84

    PubMed  CAS  Google Scholar 

  118. Åsberg M, Wägner A. Biochemical effects of antidepressant treatment — studies of monoamine metabolites in cerebrospinal fluid and platelet [3H]imipramine binding. Ciba Found Symp 1986; 123: 57–83

    PubMed  Google Scholar 

  119. Sjöström R. 5-Hydroxyindole acetic acid and homovanillic acid in cerebrospinal fluid in manic-depressive psychosis and the effect of probenecid treatment. Eur J Clin Pharmacol 1973; 6: 75–80

    PubMed  Google Scholar 

  120. Koulu M, Scheinin M, Kaarttinen A, et al. Inhibition of monoamine oxidase by moclobemide: effects on monoamine metabolism and secretion of anterior pituitary hormones and cortisol in healthy volunteers. Br J Clin Pharmacol 1989; 27: 243–55

    PubMed  CAS  Google Scholar 

  121. Dingemanse J, Korn A, Pfefen JP, et al. Biochemical effects of high single doses of moclobemide in man: correlation with plasma concentrations. Psychopharmacol 1992; 106: S46–8

    CAS  Google Scholar 

  122. Berlin I, Zimmer R, Thiede HM, et al. Comparison of the monoamine oxidase inhibiting properties of 2 reversible and selective monoamine oxidase A inhibitors moclobemide and toloxatone, and assessment of their effect on psychometric performance in healthy subjects. Br J Clin Pharmacol 1990; 30: 805–16

    PubMed  CAS  Google Scholar 

  123. Fritze J, Laux G, Sofic E, et al. Plasma moclobemide and metabolites: lack of correlation with clinical response and biogenic amines. Psychopharmacol 1989; 99: 252–6

    CAS  Google Scholar 

  124. Holford NHG, Guentert TW, Dingemanse J, et al. Monoamine oxidase-A: pharmacodynamics in humans of moclobemide, a reversible and selective inhibitor. Br J Clin Pharmacol 1994; 37: 433–9

    PubMed  CAS  Google Scholar 

  125. Eisenhofer G, Goldstein DS, Kopin IJ. Plasma dihydroxyphenylglycol for estimation of noradrenaline neuronal re-uptake in the sympathetic nervous system in vivo. Clin Sci 1989; 76: 171–82

    PubMed  CAS  Google Scholar 

  126. Fridgen B. Effect of catechol-O-methyltranferase (COMT) inhibition on the in vivo kinetics of dihydroxyphenylglycol (DOPEG), 3-methoxy-4-hydroxy-phenylglycol (MOPEG) and dihydroxyphenylalanine (DOPA). Naunyn Schmiedebergs Arch Pharmacol 1992; 345 Suppl. 1: R103

    Google Scholar 

  127. Halbruegge T, Wölfel R, Grafe KH. Plasma 3,4-dihydroxyphenylglycol as a tool to assess the role of neuronal uptake in the anaesthetized rabbit. Naunyn Schmiedebergs Arch Pharmacol 1989; 340: 726–32

    CAS  Google Scholar 

  128. Guentert TW, Stebler T, Holford NHG. Time course of moclobemide concentration and monoamine oxidase (MAO) inhibition after multiple ascending doses. Clin Pharmacol Ther 1993; 53: 179

    Google Scholar 

  129. Chen DT, Ruch R. Safety of moclobemide in clinical use. In: New perspectives in the treatment of depression. Medicine Publishing Foundation Symposium Series, 33. Toronto: Medicine Group (Canada) Ltd, 1992; 13–9

    Google Scholar 

  130. Hetzel W. Das Sicherheitsprofil von Moclobemid in klinischen Studien. In: R. Steinberg, editor. Praktische Psychiatrie — RIMA in der antidepressiven Therapie. München: Medizin Verlag, 1993; 49–63

    Google Scholar 

  131. Hilton S. Review of adverse events in association with moclobemide (Aurorix). Period to 30 June 1994. Data on file, F. Hoffmann-LaRoche, Basel, Switzerland

    Google Scholar 

  132. Hackett LP, Joyce DA, Hall RW, et al. Disposition and clinical effects of moclobemide and three of its metabolites following overdose. Drug Invest 1993: 5; 281–4

    Google Scholar 

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Authors and Affiliations

  1. College of Pharmacy, The University of Arizona, Tucson, Arizona, 85721, USA

    Michael Mayersohn

  2. Department of Clinical Pharmacology, F. Hoffmann-LaRoche Ltd., Basel, Switzerland

    Theodor W. Guentert

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  1. Michael Mayersohn
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  2. Theodor W. Guentert
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This review is dedicated to the memory of the late Mose Da Prada (1934–1995) who was instrumental in the discovery and development of moclobemide, among many other achievements in the field of monoamine pharmacology

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Mayersohn, M., Guentert, T.W. Clinical Pharmacokinetics of the Monoamine Oxidase-A Inhibitor Moclobemide. Clin-Pharmacokinet 29, 292–332 (1995). https://doi.org/10.2165/00003088-199529050-00002

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