Skip to main content
SpringerLink
Log in

Tyramine pressor sensitivity in healthy subjects during combined treatment with moclobemide and selegiline

  • Pharmacodynamics
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Objective: The objectives of this double-blind study were to assess the tolerability and i.v. tyramine pressor response during combined treatment with moclobemide and selegiline.

Subjects: Two parallel groups of 12 healthy male and female subjects were treated with 200 mg moclobemide or 5 mg selegiline b.d. for 14 days. On Day 7, selegiline or moclobemide was added to the other treatment. IV tyramine pressor tests were conducted at baseline and at steady state during mono- and combined treatment.

Results: Treatment with moclobemide and selegiline alone was well tolerated, whereas combined treatment led to a slight increase in adverse events. Tyramine pressor sensitivity during moclobemide, selegiline and moclobemide + selegiline treatment was enhanced, on average, by 2.4-, 1.3- and 8.4-times, respectively.

Conclusion: Although combined treatment with moclobemide and selegiline was well tolerated, the supra-additive potentiation of the tyramine pressor effects means that dietary restriction of tyramine intake will be necessary during such combination therapy.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Blackwell B, Marley E, Price J, Tylor D (1967) Hypertensive interactions between monoamine oxidase inhibitors and food-stuffs. Br J Psychiat 113:349–365.

    Article  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  3. Houslay MD, Tipton KF, Youdim MBH (1971) Multiple forms of monoamine oxidase, fact and artifact. Life Sci 19:467–478.

    Article  Google Scholar 

  4. Hasan F, McCrodden JM, Kennedy NP, Tipton KF (1988) The involvement of intestinal monoamine oxidase in the transport and metabolism of tyramine. J Neural Transm [Suppl] 26:1–9.

    CAS  Google Scholar 

  5. Illet KF, George CF, Davies DS (1980) The effect of monoamine oxidase inhibitors on first-pass metabolism of tyramine in dog intestine. Biochem Pharmacol 29:2551–2556.

    Article  Google Scholar 

  6. Dollery CT, Brown MJ, Davies DS, Lewis PJ, Strolin-Benedetti M (1983) Oral absorption and concentration-effect relationship of tyramine with and without cimoxatone, a type-A specific inhibitor of monoamine oxidase. Clin Pharmacol Ther 34:651–662.

    Article  CAS  PubMed  Google Scholar 

  7. Da Prada M, Kettler R, Keller HH, Burkard WP, Muggli-Manigilio D, Haefely WE (1988) Neurochemical profile of moclobemide, a short-acting and reversible inhibitor of monoamine oxidase type A. J Pharmacol Exp Ther 248:400–414.

    Google Scholar 

  8. Haefely W, Burkard WP, Cesura AM, Kettler R, Lorez HP, Martin JR, Richards JG, Scherschlicht R, Da Prada M (1992) Biochemistry and pharmacology of moclobemide, a prototype RIMA. Psychopharmacology [Suppl] 106:6–14.

    Article  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  10. Priest RG, Schmid-Burgk W (1994) Moclobemide in the treatment of depression. Rev Contemp Pharmacother 5:35–43.

    Google Scholar 

  11. Kom A, Da Prada M, Raffesberg W, Gasic S, Eichler HG (1988) Effect of moclobemide, a new reversible monoamine oxidase inhibitor, on absorption and pressor effect of tyramine. J Cardiovasc Pharmacol 11:17–23.

    Article  Google Scholar 

  12. Kom A, Da Prada M, Raffesberg W, Allen S, Gasic S (1988) Tyramine pressor effect in man: studies with moclobemide, a novel, reversible monoamine oxidase inhibitor. J Neural Transm [Suppl] 26:57–71.

    Google Scholar 

  13. Wijnands S, Chang PC, Blauw GJ, van den Krogt J, Gieschke R, Schoerlin M-P, van Brummelen P (1989) Potentiation of the pressor effect of oral and intravenous tyramine during administration of the selective MAO-A inhibitor moclobemide in healthy volunteers. J Psychopharmacol 3:36–44.

    Article  CAS  PubMed  Google Scholar 

  14. Chrisp P, Mammen GJ, Sorkin ME (1991) Selegiline. A review of its pharmacology, symptomatic benefits and protective potential in Parkinson's disease. Drugs Aging 1:228–248.

    Article  CAS  PubMed  Google Scholar 

  15. Youdim MBH, Da Prada M, Amrein R (1988) The cheese effect and new reversible MAO-A inhibitors. J Neural Transm [Suppl] 26:1–136.

    Google Scholar 

  16. Waldmeier PC, Felner AE (1978) Deprenyl: loss of selectivity for inhibition of B-type MAO after repeated treatment. Biochem Pharmacol 27:801–802.

    Article  CAS  PubMed  Google Scholar 

  17. Cummings JL (1992) Depression and Parkinson's disease. Am J Psychiat 149:443–454.

    Article  CAS  PubMed  Google Scholar 

  18. Thornton C, Dore CJ, Elsworth JD, Herbert M, Stern GM (1980) The effect of deprenyl, a selective monoamine oxidase B inhibitor, on sleep and mood in man. Psychopharmacology 70:163–166.

    Article  CAS  PubMed  Google Scholar 

  19. Bieck PR, Antonin K-H (1988) Oral tyramine pressor test and the safety of monoamine oxidase inhibitor drugs: comparison of brofaromine and tranylcypromine in healthy subjects. J Clin Psychopharmacol 8:237–245.

    Article  CAS  PubMed  Google Scholar 

  20. Guentert TW, Mayerson M (1994) Clinical-pharmacokinetic profile of moclobemide and its comparison with other MAO-inhibitors. Rev Contemp Pharmacother 5:19–34.

    Google Scholar 

  21. Bieck PR, Antonin KH, Schmidt E (1993) Clinical pharmacology of reversible monoamine oxidase-A inhibitors. Clin Neuropharmacol 16 [Suppl 2]:S34-S41.

    PubMed  Google Scholar 

  22. Felner AE, Waldmeier PC (1979) Cumulative effects of irreversible MAO inhibitors in vivo. Biochem Pharmacol 28:995–1002.

    Article  CAS  PubMed  Google Scholar 

  23. Heinonen EH, Lammintausta R (1991) A review of the pharmacology of selegiline. Acta Neurol Scand 84 [Suppl 136]:44–59.

    Article  Google Scholar 

  24. Gerlach M, Riederer P, Youdim M (1992) The molecular pharmacology of L-deprenyl. Eur J Pharmacol 226:97–108.

    Article  CAS  PubMed  Google Scholar 

  25. Sunderland T, Mueller EA, Cohen RM, Jimerson DC, Pickar D, Murphy DL (1985) Tyramine pressor sensitivity changes during deprenyl treatment. Psychopharmacology 86:432–437.

    Article  CAS  PubMed  Google Scholar 

  26. Schulz R, Antonin K-H, Hoffmann E, Jedrychowski M, Nilsson E, Schick C, Bieck PR (1989) Tyramine kinetics and pressor sensitivity during monoamine oxidase inhibition by selegiline. Clin Pharmacol Ther 46:528–536.

    Article  CAS  PubMed  Google Scholar 

  27. Neff NH, Yang HYT (1974) Another look of monoamine oxidases and the monoamine oxidase inhibitor drugs. Life Sci 14:2061–2074.

    Article  CAS  PubMed  Google Scholar 

  28. Heinonen EH, Anttila MI, Lammintausta RAS (1994) Pharmacokinetic aspects of 1-deprenyl (selegiline) and its metabolites. Clin Pharmacol Ther 56:742–749.

    Article  CAS  PubMed  Google Scholar 

  29. Dingemanse J, Kneer J, Wallnöfer A, Kettler R, Zürcher G, Koulu M, Kom A (1995) Pharmacokinetic-pharmacodynamic interactions between two selective monoamine oxidase inhibitors: moclobemide and selegiline. Clin Neuropharmacol (in press).

  30. Koulu M, Scheinin M, Kaarttinen A, Kallio J, Pyykkö K, Vuorinen J, Zimmer RH (1989) 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 27:243–255.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Youdim MBH, Finberg JPM (1986) MAO type B inhibitors as adjunct to L-Dopa therapy. Adv Neurol 45:127–136.

    Google Scholar 

  32. Lader MH, Sakalis G, Tansella M (1970) Interactions between sympathomimetic amines and a new monoamine oxidase inhibitor. Psychopharmacology 18:118–123.

    Article  CAS  Google Scholar 

  33. Reynolds GP, Elsworth JD, Blau K, Sandler M, Lees AJ, Stern GM (1978) Deprenyl is metabolised to metamphetamine and amphetamine in man. Br J Clin Pharmacol 6:542–544.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. Somerset Pharmaceuticals Inc. (1995) Package insert Eldepryl®.

Download references

Author information

Authors and Affiliations

  1. Department of Internal Medicine III, Division of Endocrinology and Metabolism, University of Vienna, Austria

    A. Korn & B. Wagner

  2. Department of Clinical Pharmacology, Hoffmann-La Roche Ltd., CH-4002, Basel, Switzerland

    J. Dingemanse & E. Moritz

Authors
  1. A. Korn
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B. Wagner
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. Dingemanse
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E. Moritz
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Korn, A., Wagner, B., Dingemanse, J. et al. Tyramine pressor sensitivity in healthy subjects during combined treatment with moclobemide and selegiline. Eur J Clin Pharmacol 49, 273–278 (1996). https://doi.org/10.1007/BF00226327

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00226327

Key words

Search

Navigation