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Effect of a reversible and selective MAO-A inhibitor (cimoxatone) on diurnal variation in plasma prolactin level in man

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Summary

Prolactin (PRL) secretion is stimulated by serotonin (5-HT) and inhibited by dopamine (DA). 5-HT is generally recognized as a substrate for type A monoamine oxidase (MAO), whereas DA is considered as a substrate for either A or B, or both forms of MAO, depending on the species and tissues used. The effect of cimoxatone, a reversible, selective MAO-A inhibitor, on diurnal variation in plasma PRL level was investigated in healthy adults after a single 40 mg oral dose, as an indirect approach to investigating whether DA is preferentially a substrate for Type A or B MAO in man. The circadian rhythm in PRL, stress conditions and diet were taken into account in the present study, which was placebo-controlled. There was a slight but significant reduction in circulating PRL in the six subjects, which persisted for at least 9 h after cimoxatone. However, the duration of the decrease in plasma PRL was shorter than the inhibition of MAO-A. The results are not inconsistent with the presence of both forms of MAO in the human hypothalamus and with DA as a substrate for both forms in this region, if it is assumed that the hypothalamic concentrations of the drug during the period 0–9 hours was sufficiently high to inhibit DA deamination by both forms of MAO.

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References

  1. Adolfsson R, Gottfries CG, Roos BE, Winblad B (1979) Postmortem distribution of dopamine and homovanillic acid in human brain, variations related to age, and review of the literature. J Neural Transm 45: 81–105

    Google Scholar 

  2. Advis JP, Simpkins JW, Bennett J, Meites J (1979) Serotoninergic control of prolactin release in male rats. Life Sci 24: 359–366

    Google Scholar 

  3. Baumann PA, Maître L (1976) Is drug inhibition of dopamine uptake a misinterpretation of in vitro experiments? Nature 264: 789–790

    Google Scholar 

  4. Ben-Jonathan N, Oliver C, Weiner HJ, Mical RS, Porter JC (1977) Dopamine in hypophysial portal plasma of the rat during the estrous cycle and throughout pregnancy. Endocrinology 100: 452–458

    Google Scholar 

  5. Chen HT, Simpkins JW, Mueller GP, Meites J (1977) Effects of pargyline on hypothalamic biogenic amines and serum prolactin, LH and TSH in male rats. Life Sci 21: 533–541

    Google Scholar 

  6. Clemens JA, Shaar J, Smalstig EB (1980) Dopamine, PIF, and other regulators of prolactin secretion. Fed Proc 39: 2907–2911

    Google Scholar 

  7. Da Prada M, Keller HH, Kettler R, Schaffner R, Pieri M, Burkard W, Korn A, Haefely W (1982) RO 11-1163, a specific and short acting MAO inhibitor with antidepressant properties. In: Kamijo K, Usdin E, Nagatsu T (eds) Monoamine oxidase, basic and clinical frontiers. Excerpta Medica, Amsterdam Oxford Princeton, International Congress Series 564, p 183

  8. Davidson L, Vandongen R, Beilin LJ (1981) Effect of eating bananas on plasma free and sulfate-conjugated catecholamines. Life Sci 29: 1773–1778

    Google Scholar 

  9. Demarest KT, Moore KE (1979) Comparison of dopamine synthesis regulation in terminals of nigrostriatal, mesolimbic tuberoinfundibular and tuberohypophyseal neurons. J Neural Transm 46: 263–277

    Google Scholar 

  10. Demarest K, Moore KE (1981) Type A monoamine oxidase catalyses the intraneuronal deamination of dopamine within nigrostriatal mesolimbic, tuberoinfundibular and tuberohypophyseal neurons in the rat. J Neural Transm 52: 175–187

    Google Scholar 

  11. De Rosa G, Corsello SM, Ruffilli MP, Della Casa S, Pasargiklian E (1981) Prolactin secretion after beer. Lancet 2: 934

    Google Scholar 

  12. Djursing H, Hagen C, Moller J, Christiansen C (1981) Short and long term fluctuations in plasma prolactin concentration in normal subjects. Acta Endocrinol 97: 1–6

    Google Scholar 

  13. Fowler CJ, Wiberg A, Oreland L, Marcusson J, Winblad B (1980) The effect of age on the activity and molecular properties of human brain monoamine oxidase. J Neural Transm 49: 1–20

    Google Scholar 

  14. Fowler CJ, Strolin Benedetti M (1983) The metabolism of dopamine by both forms of monoamine oxidase in the rat brain. J Neurochem 40: 1534–1541

    Google Scholar 

  15. Gomeni C, Gomeni R (1978) IGPHARM: interactive graphic package for pharmacokinetic analysis. Comp Biomed Res 11: 345–361

    Google Scholar 

  16. Heikkila RE, Orlansky H, Cohen G (1975) Studies on the distinction between uptake inhibition and release of [3H]-dopamine in rat brain tissue slices. Biochem Pharmacol 24: 847–852

    Google Scholar 

  17. Hökfelt T, Johansson O, Fuxe K, Elde R, Goldstein M, Park P, Efendic S, Luft R, Fraser H, Jeffcoate S (1977) Hypothalamic dopamine neurons and hypothalamic peptides. Adv Biochem Psychopharmacol 16: 99–138

    Google Scholar 

  18. Kamberi IA, Mical RS, Porter JC (1971) Effect of anterior pituitary perfusion and intraventricular injection of catecholamines on prolactin release. Endocrinology 88: 1012–1020

    Google Scholar 

  19. Kan JP, Strolin Benedetti M (1980) Antagonism between long acting monoamine oxidase inhibitors (MAO I) and MD 780515, a new specific and reversible MAO I. Life Sci 26: 2165–2171

    Google Scholar 

  20. Kan JP, Strolin Benedetti M (1981) Characteristics of the inhibition of rat brain monoamine oxidase ‘in vitro’ by MD 780515. J Neurochem 36: 1561–1571

    Google Scholar 

  21. Keane PE, Menager J, Strolin Benedetti M (1981) The effect of monoamine oxidase A and B inhibitors on rat serum prolactin. Neuropharmacology 20: 1157–1162

    Google Scholar 

  22. Lichtensteiger W (1979) The neuroendocrinology of dopamine systems. In: Horn AS, Korf J, Westerink BHC (eds) The neurobiology of dopamine. Academic Press, London New York San Francisco, p 491

    Google Scholar 

  23. Lu KH, Meites J (1971) Inhibition by 1-Dopa and monoamine oxidase inhibitors of pituitary prolactin release; stimulation by methyldopa and d-amphetamine Proc Soc Exp Biol Med 137: 480–483

    Google Scholar 

  24. Lu KH, Meites J (1973) Effects of serotonin precursors and melatonin on serum prolactin release in rats. Endocrinology 93: 152–155

    Google Scholar 

  25. MacKay AVP, Davies P, Dewar AJ, Yates CM (1978) Regional distribution of enzymes associated with neurotransmission by monoamines, acetylcholine and gaba in the human brain. J Neurochem 30: 827–839

    Google Scholar 

  26. MacLeod RM (1976) Regulation of prolactin secretion. In: Martini L, Ganong WF (eds) Frontiers in neuroendocrinology, vol IV. Raven Press, New York, p 169

    Google Scholar 

  27. Marley E (1977) Monoamine oxidase inhibitors and drug interactions. In: Grahame-Smith DG (ed) Drug interactions. Biological Council, London, p 171

    Google Scholar 

  28. Meek JL, Neff NH, (1972) Fluorimetric estimation of 4-hydroxy-3-methoxyphenylethyleneglycol sulphate in brain. Br J Pharmacol 45: 435–441

    Google Scholar 

  29. Meltzer HY, Bush DA, Robertson A, Tricou BJ, Fang VS (1981) Prolactin secretion: an update. Psychopharmacol Bull 17 (3): 168–171

    Google Scholar 

  30. Mendlewicz J, Youdim MBH (1977) Monoamine oxidase inhibitors and prolactin secretion. Lancet 2: 507

    Google Scholar 

  31. Mendlewicz J, Van Cauter E, Linkowski P, L'Hermite M, Robyn C (1980) The 24-h profile of prolactin depression. Life Sci 27: 2015–2024

    Google Scholar 

  32. Mornex R, Jordan D (1980) Serotonin and endocrine rhythms. Biomedicine 32: 163–165

    Google Scholar 

  33. O'Carroll AM, Fowler CJ, Phillips JP, Tobias I, Tipton KF (1983) The deamination of dopamine by human brain monoamine oxidase. Specificities for the two enzyme forms in seven brain regions. Naunyn-Schmiedeberg's Arch Pharmacol 322: 198–202

    Google Scholar 

  34. Owen F, Cross AJ, Lofthouse R, Glover V (1979) Distribution and inhibition characteristics of human brain monoamine oxidase. Biochem Pharmacol 40: 1077–1080

    Google Scholar 

  35. Pilotte NS, Porter JC (1981) Dopamine in hypophysial portal plasma and prolactin in systemic plasma of rats treated with 5-hydroxytryptamine. Endocrinology 108: 2137–2141

    Google Scholar 

  36. Poirier MF, Olié JP, Loo H, Deniker P, Strolin Benedetti M, Rovei V, Languillat JM (1982) La cimoxatone (MD 780515), un nouvel IMAO-A réversible: résultats préliminaires d'une étude clinique, pharmacocinétique et biochimique chez 10 patients déprimés. Association Mondiale de Psychiatrie, Société Marocaine de Psychiatrie, Symposium Régional, Marrakech, Oct 31–Nov 4. Abstract book, p 117

  37. Poirier MF, Olié JP, Loo H, Deniker P, Strolin Benedetti M, Rovei V, Lesage A (1983) Activité antidépressive, caractéristiques pharmacocinétiques et propriétés biochimiques de la cimoxatone, un nouvel IMAO-A réversible. L'Encéphale, in press

  38. Quigley ME, Yen SSC (1979) A mid-day surge in cortisol levels. J Clin Endocrinol Metab 49 (6): 945–947

    Google Scholar 

  39. Quigley ME, Ropert JF, Yen SSC (1981) Acute prolactin release triggered by feeding. J Clin Endocrinol Metab 52 [5]: 1043–1045

    Google Scholar 

  40. Riederer P, Reynolds GP, Youdim MBH, Jellinger K (1982) In vitro tests of MAO inhibitors in human brain tissue: chemical structure and pharmacological action. In: Kamijo K, Usdin E, Nagatsu T (eds) Monoamine oxidase, basic and clinical frontiers. Excerpta Medica, Amsterdam Oxford Princeton, International Congress Series 564, p 345

  41. Rovei V, Rigal M, Sanjuan M, Thiola A (1983a) High-performance liquid chromatographic determination of cimoxatone and its O-demethyl metabolite in plasma. J Chromatogr 277: 391–395

    Google Scholar 

  42. Rovei V, Mitchard M, Strolin Benedetti M, Kendall MJ (1983b) Pharmacokinetic and relative bioavailability studies of cimoxatone in humans. Int J Clin Pharmacol Ther Toxicol (in press)

  43. Sassin JF, Frantz AG, Weitzman ED, Kapen S (1972) Human prolactin: 24-hour pattern with increased release during sleep. Science 177: 1205–1207

    Google Scholar 

  44. Slater SL, Lipper S, Shilling DJ, Murphy DL (1977) Elevation of plasma prolactin by monoamine oxidase inhibitors. Lancet 2: 275–276

    Google Scholar 

  45. Strolin Benedetti M, Kan JP, Keane PE (1980) Biochemical evidence for specific and reversible inhibition of Type A monoamine oxidase by MD 780515. 12th CINP Congr., Göteborg, Sweden. Abstract book, p 332. Supplement to Progr Neuropsychopharmacol, Radouco-Thomas C, Garcin F (eds). Pergamon Press

  46. Strolin Benedetti M, Chanoine F, Rovei V, Zini R, Tillement JP (1981) Plasma protein binding in vivo and in vitro of the reversible Type A MAO inhibitor MD 780515. Abstract book, p 554. 8th Int Congr Pharmacol Tokyo, 1981 Iuphar, Japan

  47. Tuomisto J (1978) Neuropharmacological inervention of the pituitary-hypothalamic relationship. Ann Clin Res 10: 120–132

    Google Scholar 

  48. Young M (1981) The significance of biogenic amines in food and beverages. Aust J Pharm Sci 10: 1–8

    Google Scholar 

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Authors and Affiliations

  1. Centre de Recherche Delalande, Rueil-Malmaison, France

    M. Strolin Benedetti, A. Lesage, V. Rovei & P. Dostert

  2. Laboratoire de Pharmacologie Médicale, INSERM U-195, Faculté de Médecine, Clermont-Ferrand, France

    A. Eschalier

  3. Clinique Neurologique, Clermont-Ferrand, France

    G. Dordain

  4. Service de Psychiatrie A, CHU de Clermont-Ferrand, Clermont-Ferrand, France

    E. Zarifian

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  1. M. Strolin Benedetti
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  2. A. Eschalier
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  3. A. Lesage
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  5. V. Rovei
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Strolin Benedetti, M., Eschalier, A., Lesage, A. et al. Effect of a reversible and selective MAO-A inhibitor (cimoxatone) on diurnal variation in plasma prolactin level in man. Eur J Clin Pharmacol 26, 71–77 (1984). https://doi.org/10.1007/BF00546712

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  • DOI: https://doi.org/10.1007/BF00546712

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