Advertisement

Biochemical pharmacology of befloxatone (MD370503), a new potent reversible MAO-A inhibitor

  • V. Rovei
  • D. Caille
  • O. Curet
  • D. Ego
  • F.-X. Jarreau
Conference paper
Part of the Journal of Neural Transmission book series (NEURAL SUPPL, volume 41)

Summary

In vitro and ex-vivo studies show that befloxatone, a new oxazolidinone derivative, is a potent, reversible, competitive and specific MAO-A inhibitor (KiA from 1.9 to 3.6 nM and KiB/KiA ratio between 100 and 400, in the Rat and in Man, depending on the tissue). Befloxatone possesses a marked activity in antidepressant-sensitive behavioral models in rats (from 0.03 to 0.15 mg/kg po) and mice (from 0.21 to 0.29 mg/kg po). At these doses, befloxatone does not induce a significant potentiation of oral tyramine. Befloxatone is devoid of sedative, anticholinergic and cardiovascular effects. Befloxatone is rapidly and extensively distributed in rat brain, the pharmacokinetics are linear in the rat and in man in a large range of doses. Befloxatone is well tolerated in healthy volunteers and is developed as an antidepressant.

Keywords

Forced Swimming Test Amine Oxidase Biochemical Pharmacology Semicarbazide Sensitive Amine Oxidase Learn Helplessness Paradigm 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Amrein R, Allen SR, Vranesic D, Stabl M (1988) Antidepressant drug threrapy: associated risks. J Neural Transm [Suppl] 26: 73–86.Google Scholar
  2. Ansseau M, Caillé P, Derks C, Cieren-Puiseux I, Soubrane C, Wauthy J, Ego D, Curet O, Thiola A, Rovei V, Jarreau FX (1992a) Phase I study of single ascending doses of Befloxatone, a new reversible MAO-A inhibitor antidepressant. Proceedings XVIII CINP, Nice. Clin Neuropharmacol 15: 328B.Google Scholar
  3. Ansseau M, Caillé P, Derks C, Cieren-Puiseux I, Soubrane C, Wauthy J, Ego D, Rovei V, Jarreau FX (1992b) Phase I study of repeated doses of Befloxatone, a new reversible MAO-A inhibitor antidepressant. Proceedings XVIII CINP, Nice. Clin Neuropharmacol 15: 328B.Google Scholar
  4. Bieck PR, Antonin KH (1989) Tyramine potentiation during treatment with MAO inhibitors: brofaromine and moclobemide vs irreversible inhibitors. J Neural Transm [Suppl] 28: 21–31.Google Scholar
  5. Callingham BA (1992) Possible drug interactions with reversible MAO inhibitors. Proc XVIII CINP Nice 1992. Clin Neuropharmacol [Suppl 1] 15: 71–225.Google Scholar
  6. Curet O, Damoiseau G, Labaune JP, Rovei V, Jarreau FX (1992) Effects of befloxatone, a new potent reversible MAO-A inhibitor, on cortex and striatum monoamines in freely moving rats. 5th International Amine Oxidase Workshop, Galway (Ireland) (unpublished).Google Scholar
  7. Da Prada M, Zurcher G, Wutrich I, Haefely WE (1988) On tyramine, food, beverages and the reversible MAO inhibitor moclobemide. J Neural Transm 26: 31–56.Google Scholar
  8. Ego D, Parisy D, Pattano N (1992) Pharmacokinetics of befloxatone, a new reversible inhibitor of MAO-A in rat. Proceedings XVII CINP Nice. Clin Neuropharmacol 15: 422B.CrossRefGoogle Scholar
  9. Ferrey G, Rovei V, Strolin Benedetti M, Gomeni C, Languillat JM (1985) Antidepressant activity of toloxatone, a selective MAO-A inhibitor, in depressed patients. In: Burrows GD, Norman TR, Dennerstein L (eds) Clinical and pharmacological studies in psychiatric disorders. John Libbey, London Paris, pp 83–86.Google Scholar
  10. Fitton A, Faulds D, Goa KL (1992) Moclobemide, a review of its pharmacological properties and therapeutic use in depressive illness. Drugs 43: 561–596.PubMedCrossRefGoogle Scholar
  11. Jarrott B, Vajda FJE (1987) The current status of monoamine oxidase and its inhibitors. Med J Aus 146: 634–638.Google Scholar
  12. Nutt D, Glue P (1989) Monoamine oxidase inhibitors: rehabilitation from recent research?. Br J Psychiatry 154: 287–291.PubMedCrossRefGoogle Scholar
  13. Paykel ES (1992) Role of monoamine oxidase inhibitors in the treatment of affective disorders. Proc 5th World Congress Biological Psychiatry Florence 1991. Royal Society of Medicine Services, London New York, pp 1–8.Google Scholar
  14. Rovei V, Ego D, Jarreau FX (1990) Assessment of the interaction between Humoryl (Toloxatone) and oral tyramine in man vol 1. XVII CINP, Kyoto, p 43.Google Scholar
  15. Tyrer P, Harrison-Read P (1990) New perspectives in treatment with monoamine oxidase inhibitors. Int Rev Psychiatry 2: 331–340.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • V. Rovei
    • 1
  • D. Caille
    • 1
  • O. Curet
    • 1
  • D. Ego
    • 1
  • F.-X. Jarreau
    • 1
  1. 1.Synthelabo RechercheRueil MalmaisonFrance

Personalised recommendations