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. 2006 Jun 7;8(3):283–308. doi: 10.1111/j.1527-3458.2002.tb00229.x

Moclobemide: Evolution, Pharmacodynamic, and Pharmacokinetic Properties

Udo Bonnet 1,✉
PMCID: PMC6741699  PMID: 12353059

ABSTRACT

The benzamide moclobemide is a reversible inhibitor of monoamine‐oxidase‐A (RIMA). It has been extensively evaluated in the treatment of a wide spectrum of depressive disorders and less extensively in anxiety disorders. While clinical aspects will be presented in a subsequent review, this article focuses primarily on moclobemide's evolution, pharmacodynamic and pharmacokinetic properties. In particular, the effects on neurotransmission and intracellular signal transduction, the neuroendocrine system, the tyramine pressure response and animal models of depression are surveyed. In addition, other CNS effects are reviewed with special respect to experimental serotonergic syndrome, anxiolytic and antinociceptive activity, sleep, cognition and driving performance, neuroprotection and seizures.

Keywords: Anxiety, Depression, MAO inhibitors, Moclobemide

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References

  • 1. Alemany R, Olmos G, Garcia‐Sevilla JA. The effects of phenelzine and other monoamine oxidase inhibitor antidepressants on brain and liver I2 imidazoline‐preferring receptors. Br J Pharmacol 1995;114:837–845. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2. Allain H, Lieury A, Brunet‐Bourgin F, et al. Antidepressants and cognition: Comparative effects of moclobemide, viloxazine and maprotiline. Psychopharmacology 1992;106:S56–S61. [DOI] [PubMed] [Google Scholar]
  • 3. Amrein R, Martin JR, Cameron AM. Moclobemide in patients with dementia and depression. Adv Neurol 1999;80:509–519. [PubMed] [Google Scholar]
  • 4. Anand R, Wesnes KA. Cognition‐enhancing effects of moclobemide, a reversible MAO inhibitor, in humans. Adv Neurol 1990;51:261–268. [PubMed] [Google Scholar]
  • 5. Ananth J, Luchins D. A review of combined tricyclic and MAOI therapy. Comprehensive Psychiatry 1977;18:221–230. [DOI] [PubMed] [Google Scholar]
  • 6. Arai R, Horiike K, Hasegawa Y. Dopamine‐degrading activity of monoamine oxidase is not detected by histochemistry in neurons of the substantia nigra pars compacta of the rat. Brain Res 1998;812:275–278. [DOI] [PubMed] [Google Scholar]
  • 7. 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;49:522–527. [DOI] [PubMed] [Google Scholar]
  • 8. Bach AJB, Lan NC, Johnson DL, et al. cDNA cloning of human liver monoamine oxidase A and B: Molecular basis of differences in enzymatic properties. Proc Natl Acad Sci USA 1988;85:4934–4938. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9. Baker GB, Urichuk LJ, McKenna KF, et al. Metabolism of monoamine oxidase inhibitors. Cell Mol Neurobiol 1999;19:411–426. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10. Bergström M, Westerberg G, Langström B. 11C‐Harmine as a tracer for monoamine oxidase A (MAO‐A): In vitro and in vivo studies. Nucl Med Biol 1997;24:287–293. [DOI] [PubMed] [Google Scholar]
  • 11. Bergström M, Westerberg G, Németh G, et al. MAO‐A inhibition in brain after dosing with esuprone, moclobemide and placebo in healthy volunteers: In vivo studies with positron emission tomography. Eur J Clin Pharmacol 1997;52:121–128. [DOI] [PubMed] [Google Scholar]
  • 12. Berlin I, Zimmer C, Cournot A, et al. Determination and comparison of the pressure effect of tyramine during long‐term moclobemide and tranylcypromine treatment in healthy volunteers. Clin Pharmacol Ther 1989;46:344–351. [DOI] [PubMed] [Google Scholar]
  • 13. Berlin I, Zimmer R, Thiede HM, et al. Comparison of the monoamine oxidase inhibiting properties of two reversible and selective monoamine oxidase‐A inhibitors moclobemide and toloxatone, an assessment of their effect on psychometric performance in healthy subjects. Br J Clin Pharmacol 1990;30:805–816. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14. Berlin I, Said S, Spreux‐Varoquaux O, et al. Monoamine oxidase A and B activities in heavy smokers. Biol Psychiatry 1995;38:756–761. [DOI] [PubMed] [Google Scholar]
  • 15. Biek PR, Antonin K‐H. Tyramine potentiaton during treatment with MAO inhibitors: brofaromine, and moclobemide vs. irreversible inhibitors. J Neural Transm 1989;28 (Suppl): 21–31. [PubMed] [Google Scholar]
  • 16. Bjartmar L, Johansson IM, Ross SB, et al. Selective effects on NGFI‐A, MR, GR, and NGFI‐B hippocampal mRNA expression after chronic treatment with different subclasses of antidepressants in the rat. Psychopharmacology 2000;151:7–12. [DOI] [PubMed] [Google Scholar]
  • 17. Blackwell B. Monoamine oxidase inhibitor interactions with other drugs. J Clin Psychopharmacol 1991;11:55–59. [PubMed] [Google Scholar]
  • 18. Blois R, Gaillard JM. Effects of moclobemide on sleep in healthy human subjects. Acta Psychiatr Scand 1990:82 (Suppl 360): 73–75. [DOI] [PubMed] [Google Scholar]
  • 19. Bonnet U, Wiemann M. Ammonium prepulse: Effects on intracellular pH and bioelectric activity of CA3‐neurones in guinea‐pig hippocampal slices. Brain Res 1999;840:16–22. [DOI] [PubMed] [Google Scholar]
  • 20. Bonnet U, Leniger T, Wiemann M. Moclobemide reduces intracellular pH and neuronal activity of CA3 neurones in guinea‐pig hippocampal slices — implication for its neuroprotective properties. Neuropharmacology 2000;39:2067–2074. [DOI] [PubMed] [Google Scholar]
  • 21. Bonnet U, Wiemann M, Bingmann D. Intracellular pH modulates spontaneous and epileptiform bioelectric activity of hippocampal CA3‐neurones. Eur Neuropsychopharmacol 2000;97:97–103. [DOI] [PubMed] [Google Scholar]
  • 22. Bonnet U, Büsselberg D, Wiemann M. MAO‐inhibition is associated with a modest neuronal acidification. Pharmacopsychiatry 2001;34:165. [Google Scholar]
  • 23. Bonnet U. Moclobemide: Therapeutic Use and Clinical Studies. CNS Drug Rev; In press. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24. Bonnet U, Bingmann D, Leniger T, et al. Valproate acidifies hippocampal CA3 neurones — a novel mode of action. Eur Neuropsychopharmacol 2002;12:279–285. [DOI] [PubMed] [Google Scholar]
  • 25. Bousquet P, Feldmann J. Drugs acting on imidazoline receptors. A review of their pharmacology, their use in blood pressure control and their potential interest in cardioprotection. Drugs 1999;58:799–812. [DOI] [PubMed] [Google Scholar]
  • 26. Brodie BB, Bickel MH, Sulser F. Desimipramine, a new type of antidepressant drug. Med Exp 1961;5:454–458. [DOI] [PubMed] [Google Scholar]
  • 27. Burkard WP, Bonetti EP, Da Prada M, et al. Pharmacological profile of moclobemide, a short‐acting and reversible inhibitor of monoamine oxidase type A. J Pharmacol Exp Ther 1989;248:391–399. [PubMed] [Google Scholar]
  • 28. Burrows GD, Da Prada M (eds). Reversible MAO‐A inhibitors as antidepressants — basic advances and clinical perspectives. J Neural Transm 1989;Suppl 28:1–103. [PubMed] [Google Scholar]
  • 29. Cocio S. Metabolism of the newer antidepressants. An overview of the pharmacological and pharmacokinetic implications. Clin Pharmacokinet 1998;34:281–302. [DOI] [PubMed] [Google Scholar]
  • 30. Callingham BA, Ovens RS. Some in vitro effects of moclobemide and other MAO inhibitors on responses to sympathomimetic amines. J Neural Transm 1987;26:17–29. [PubMed] [Google Scholar]
  • 31. Cao Danh H, Strolin Benedetti M, et al. Differential changes in monoamine oxidase A and B activity in aging rat tissues In: Tripton KF, Dostert P, Strolin Benedetti M, Eds. Monoamine oxidase and disease. Prospects for therapy with reversible inhibitors. London : Academic Press, 1984:301–317. [Google Scholar]
  • 32. Cesura AM, Pletscher A. The new generation of monoamine oxidase inhibitors. Progr Drug Res 1992;38:171–297. [DOI] [PubMed] [Google Scholar]
  • 33. Codoz D, Porchert HC, Dayer P. Central analgesic effects of desimipramine, fluvoxamine, and moclobemide after single oral dosing: A study in healthy volunteers. Clin Pharmacol Ther 1993;54:339–344. [DOI] [PubMed] [Google Scholar]
  • 34. Colzi A, D'Agostini F, Cesura AM, et al. Brain microdialysis in rats: A technique to reveal competition in vivo between endogeneous dopamine and moclobemide, a RIMA antidepressant. Psychopharmacology 1992;106:S17–S20. [DOI] [PubMed] [Google Scholar]
  • 35. Crane GE. Iproniazid (Marsilin®) phosphate, a therapeutic agent for mental disorders and debilitating diseases. Psych Res Rep Am Psych Ass 1957;8:142–152. [PubMed] [Google Scholar]
  • 36. Da Prada, M , Zürcher G, Wüthrich I, et al. On tyramine, food, beverages, and reversible MAO inhibitor moclobemide. J Neural Transm 1988;26 (Suppl): 31–36. [PubMed] [Google Scholar]
  • 37. 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;248:400–414. [PubMed] [Google Scholar]
  • 38. Da Prada M, Kettler R, Burkhard WP, et al. Some basic aspects of reversible inhibitors of monoamie oxidase‐A. Acta Psychiatr Scand 1990;82 (Suppl 360): 7–12. [DOI] [PubMed] [Google Scholar]
  • 39. Da Prada M, Zürcher G. Tyramine content of preserved and fermented foods or condiments of Far Eastern cuisine. Psychopharmacology 1992;106:S32–S34. [DOI] [PubMed] [Google Scholar]
  • 40. Da Prada, Pieri L, Cesura AM, et al. The pharmacology of moclobemide. Rev Contemp Pharmacother 1994;5:1–18. [Google Scholar]
  • 41. DeLorenzo RJ, Dashefsky LH. Anticonvulsants. Handb Neurochem 1985;9:363–403. [Google Scholar]
  • 42. Dingemanse J, Korn A, Pfefen J‐P, et al. Biochemical effects of high single doses of moclobemide in man: Correlation with plasma concentrations. Psychopharmacology 1992;106:S46–S48. [DOI] [PubMed] [Google Scholar]
  • 43. Dingemanse J, Berlin I, Payan C, et al. Comparative investigation of the effect of moclobemide and toloxatone on monoamine oxidase activity and psychomotor performance in healthy subjects. Psychopharmacology 1992;106:S68–S70. [DOI] [PubMed] [Google Scholar]
  • 44. Dingemanse J, Wood N, Guentert T, et al. Clinical pharmacology of moclobemide during chronic administration of high doses to healthy subjects. Psychopharmacology 1998;140:164–172. [DOI] [PubMed] [Google Scholar]
  • 45. Dingemanse J, Wallnöfer A, Gieschke R, et al. Pharmacokinetic and pharmacodynamic interactions between fluoxetine and moclobemide in the investigation of the “serotonin syndrome. Clin Pharmacol Ther 1998;63:403–413. [DOI] [PubMed] [Google Scholar]
  • 46. Duman RS, Heninger GR, Nestler EJ. A molecular and cellular theory of depression. Arch Gen Psychiatry 1997;54:597–606. [DOI] [PubMed] [Google Scholar]
  • 47. Eisenhofer G, Goldstein DS, Ropchak TG, et al. Source and physiological significance of plasma 3,4‐di‐hydroxyphenylglycol and 3‐methoxy‐4‐hydroxyphenylglycol. J Auton Nerv Syst 1988;24:1–14. [DOI] [PubMed] [Google Scholar]
  • 48. Eisenhofer G, Bush JE, Cannon RI, et al. Plasma dihydroxyphenylalanine and total body and regional norad‐renergic activity in humans. J Clin Endocrinol Metab 1989;68:247–255. [DOI] [PubMed] [Google Scholar]
  • 49. Eisenhofer G, Pecorella W, Pacak K, et al. The neuronal and extraneuronal origins of plasma 3‐methoxy‐4‐hydroxyphenylglycol in rats. J Nerv Auton Syst 1994;50:93–107. [DOI] [PubMed] [Google Scholar]
  • 50. Ekblom J, Tottmar O, Oreland L. Cytoprotection by deprenyl and tocapone in a cell culture model of cerebral ischemia. Pharmacol Toxicol 1998;83:194–199. [DOI] [PubMed] [Google Scholar]
  • 51. Fairweather DB, Hindmarch I. The behavioural toxicity of reversible inhibitors of monoamine oxidase A: Laboratory and clinical investigations. J Clin Psychopharmacol 1995;15 (Suppl 2): 68S–75S. [DOI] [PubMed] [Google Scholar]
  • 52. Finberg JP, Youdim MBH. Potentiation of tyramine pressor responses in conscious rats by reversible inhibitors of monoamine oxidase. J Neural Transm 1987;26:11–16. [PubMed] [Google Scholar]
  • 53. Finberg JPM. Pharmacology of reversible and selective inhibitors of monoamine oxidase type A. Acta Psychiatr Scand 1995;91 (Suppl 386): 8–13. [DOI] [PubMed] [Google Scholar]
  • 54. Fitton A, Faulds D, Goa KL. Moclobemide — a review of its pharmacological properties and therapeutic use in depressive illness. Drugs 1992;43:561–596. [DOI] [PubMed] [Google Scholar]
  • 55. Fitzgerald LW, Kaplinsky L, Kimelberg HK. Serotonin metabolism by monoamine oxidase in rat primary astrocyte cultures. J Neurochem 1990;55:2008–2014. [DOI] [PubMed] [Google Scholar]
  • 56. Fowler JS, Volkow ND, Wang GJ, et al. Brain monoamine oxidase A inhibition in cigarrete smokers. Proc Natl Acad Sci USA 1996;93:14065–14069. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 57. Frazer A. Antidepressants. J Clin Psychiatry 1997;58 (Suppl 6): 9–25. [PubMed] [Google Scholar]
  • 58. Freeman H. Moclobemide. Lancet 1993;342:1528–1532. [DOI] [PubMed] [Google Scholar]
  • 59. Fritze J, Laux G, Sofic E, et al. Plasma moclobemide and metabolites: Lack of correlation with clinical response and biogenic amines phycharmacology 1989;99:252–256. [DOI] [PubMed] [Google Scholar]
  • 60. Fulton B, Benfield P. Moclobemide — an update of its pharmacological properties and therapeutic use. Drugs 1996;52:450–474. [DOI] [PubMed] [Google Scholar]
  • 61. Galderisi S, Mucci A, Bucci P, et al. Influence of moclobemide on cognitive functions of nine depressed patients: Pilot trial with neurophysiological and neuropsychological indices. Neuropsychobiology 1996;33:48–58. [DOI] [PubMed] [Google Scholar]
  • 62. Galva MD, Bondiolotti GP, Olasmaa M, et al. Effect of aging on lazabemide binding, monoamine oxidase activity and monoamine metabolites in human frontal cortex. J Neural Transm 1995;101:3–94. [DOI] [PubMed] [Google Scholar]
  • 63. 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;420:110–120. [DOI] [PubMed] [Google Scholar]
  • 64. Gex‐Fabry M, Balant‐Gorgia AE, Balant LP. Potential of concentration monitoring data for a short half‐life drug: Analysis of pharmacokinetic variability for moclobemide. Ther Drug Monit 1995;17:36–46. [DOI] [PubMed] [Google Scholar]
  • 65. Gieschke R, Schmidt‐Burgk W, Amrein R. Interaction of moclobemide, a new reversible monoamine oxidase inhibitor with oral tyramine. J Neural Transm 1987;26:97–104. [PubMed] [Google Scholar]
  • 66. Gleiter CH, Nilsson E, Antonin KH, et al. Effect of MAO inhibitors (brofaromine, clorgyline and moclobemide) on human platelet MAO‐B activity. Clin Pharmacol Ther 1990;47:165. [DOI] [PubMed] [Google Scholar]
  • 67. Goldina OA, Valdman AV. Anticonvulsant effect of some psychotropic drugs and benzamide derivatives with regard to antimonoamine oxidase activity. Eur Neuropsychopharmacol 1994;4:446–447. [Google Scholar]
  • 68. Goodnick PJ. Pharmacokinetic optimization of therapy with newer antidepressants. Clin Pharmacokinet 1994;27:307–330. [DOI] [PubMed] [Google Scholar]
  • 69. Gram LF, Brosen K. Moclobemide treatment causes a substantial rise in the sparteine metabolic ratio. Br J Clin Pharmacol 1993;35:649–652. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 70. Gram LF, Guentert TW, Grange S, et al. Moclobemide, a substrate of CYP2C19 and an inhibitor of CYP2C19, CYP2D6, and CYP1A2: Apanel study. Clin Pharmacol Ther 1995;57:670–677. [DOI] [PubMed] [Google Scholar]
  • 71. Griebel G, Perrault G, Sanger DJ. Behavioural profiles of the reversible monoamine‐oxidase inhibitors befloxatone and moclobemide in an experimental model for screening anxiolytic and antipanic drugs. Psychopharmacology 1997;131:180–186. [DOI] [PubMed] [Google Scholar]
  • 72. Guentert TW, Banken L, Hilton S, et al. Moclobemide: relationships between dose, drug concentration in plasma, and occurrence of adverse events. J Clin Psychopharmacol 1995;15 (Suppl 2): 84S–94S. [DOI] [PubMed] [Google Scholar]
  • 73. Haefely W, Burkard WP, Cesura AM, et al. Biochemistry and pharmacology of moclobemide, a prototype RIMA. Psychopharmacology 1992;106:S6–S14. [DOI] [PubMed] [Google Scholar]
  • 74. Haefely W, Burkard WP, Cesura A, et al. Pharmacology of moclobemide. Clin Neuropharmacol 1993;16 (Suppl 2): S8–S18. [PubMed] [Google Scholar]
  • 75. Härtter S, Dingemanse J, Baier D, et al. The role of cytochrome P450 2D6 in the metabolism of moclobemide. Eur Neuropharmacol 1996;6:225–230. [DOI] [PubMed] [Google Scholar]
  • 76. Haring C, Baier D, Herberg KW. Verkehrstüchtigkeit unter Moclobemid. Münchener Med Wochenschrift 1995;137:217–222. [Google Scholar]
  • 77. Harro J, Oreland L. Depression as a spreading neuronal adjustment disorder. Eur Neuropsychopharmacol 1996;6:207–223. [DOI] [PubMed] [Google Scholar]
  • 78. Hartley Z, Dubinski JM. Changes in intracellular pH associated with glutamate excitotoxicity. J Neurosci 1993;13:4690–4699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 79. Hasan F, McCrodden JM, Kennedy NP, et al. The involvement of intestinal monoamine oxidase in the transport and metabolism of tyramine. J Neural Transm 1988;26(Suppl): 1–9. [PubMed] [Google Scholar]
  • 80. Hida T, Arai R. Monoamine oxidase activity in noradrenaline neurons of locus coeruleus of the rat. A double‐labeling histochemical study. Brain Res 1998;814:209–212. [DOI] [PubMed] [Google Scholar]
  • 81. Hartter S. Wetzel H, Hammes E, Torkzadeh M, Hiemke C. Serum concentrations of fluvoxamine and clinical effects. A prospective open clinical trial. Pharmacopsychiatry 1998;31:199–200. [DOI] [PubMed] [Google Scholar]
  • 82. Hindmarch I, Kerr J. Behavioural toxicity of antidepressants with particular reference to moclobemide. Psychopharmacology 1992;106:S49–S55. [DOI] [PubMed] [Google Scholar]
  • 83. Hindmarch I, Kerr JS, Fairweather DB. The effects of moclobemide on psychomotor performance and cognitive function in the elderly. Dementia 1992;3:355–359. [DOI] [PubMed] [Google Scholar]
  • 84. Hoff P, Golling H, Kampfhammer HP, et al. Cimoxatone and moclobemide, two new MAO inhibitors: Influence in sleep parameters in patients with major depressive disorder. Pharmacopsychiatry 1986;19:249–250. [Google Scholar]
  • 85. Holford NHG, Guenter TW, Dingsemanse J, et al. Monoamine oxidase A: Pharmacodynamics in humans of moclobemide, a reversible and selective inhibitor. Br J Clin Pharmacol 1994;37:433–439. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 86. Holsboer F. Neuroendocrinology of mood disorders In: Bloom FE, Kupfer DJ. (eds). Psychopharmacology: The fourth generation of progress. New York : Raven Press, 1995:957–969. [Google Scholar]
  • 87. Hoskins JM, Gross AS, Shenfield GM, et al. High‐performance liquid chromatography‐electrospray ionization mass spectrometry method for the measurements of moclobemide and two of its metabolites in plasma. J Chromatogr B Biomed Sci Appl 2001;754:319–326. [DOI] [PubMed] [Google Scholar]
  • 88. Hosseini AR, Jackman GP, King PR, et al. Pharmacology and subcellular distribution of [3H]rilmenidine binding sites in rat brain. J Auton Nerv Syst 1988;72:129–136. [DOI] [PubMed] [Google Scholar]
  • 89. Hough CJ, Chuang D‐M. The mitochondrial hypothesis of bipolar disorder. Bipolar Disord 2000;2:145–147. [DOI] [PubMed] [Google Scholar]
  • 90. Hirsch SR, Jolley AG, Barnes TR, et al. Dysphoric and depressive symptoms in chronic schizophrenia. Schizophr Res 1989;2:259–264. [DOI] [PubMed] [Google Scholar]
  • 91. Jakobs BL. Animal behavior model for study central serotonergic synapses. Life Sci 1976;19:777–786. [DOI] [PubMed] [Google Scholar]
  • 92. Jauch R, Griesser E, Oesterhelt G, et al. Biotransformation of moclobemide in humans. Acta Psychiatr Scand 1990;82 (Suppl 360): 87–90. [DOI] [PubMed] [Google Scholar]
  • 93. Juruena MF, Pires ML, Calil HM. Moclobemide effects on prolactin plasma levels in healthy individuals: The hormonal increase induced by a single dose is maintained during a 4‐week period of drug intake. Int Clin Psychopharmacol 1997;12:317–321. [PubMed] [Google Scholar]
  • 94. Kaila K. Ionic basis of GABAA receptor channel function in the nervous system. Progr Neurobiol 1994;42:489–537. [DOI] [PubMed] [Google Scholar]
  • 95. Kato T, Kato N. Mitochondrial dysfunction in bipolar disorder. Bipolar Disord 2000;2:180–190. [DOI] [PubMed] [Google Scholar]
  • 96. Kettler R, Da Prada M, Burkard WP. Comparison of monoamine oxidase‐A inhibition by moclobemide in vitro and ex vivo in rats. Acta Psychiatr Scand 1990;82 (Suppl 360): 101–102. [DOI] [PubMed] [Google Scholar]
  • 97. Klimek V, Nowak G, Zak J, et al. The effect of repeated treatment with bofaromine, moclobemide and deprenyl on α1‐adrenergic and dopaminergic receptors in rat brain. Neurosci Lett 1990;108:189–194. [DOI] [PubMed] [Google Scholar]
  • 98. Kochersberger LM, Parker EL, Siciliano M, et al. Assignment of genes for human monoamine oxidase A and B to X chromosome. J Neurosci Res 1986;16:601–619. [DOI] [PubMed] [Google Scholar]
  • 99. Korn A, Da Prada M, Faffesberg W, et al. Tyramine pressure effect in man: Studies with moclobemide, a novel, reversible monoamine oxidase inhibitor. J Neural Transm 1988;26 (Suppl): 57–71. [PubMed] [Google Scholar]
  • 100. 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;27:243–255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 101. Lalies MD, Hibell A, Hudson AL, et al. Inhibition of central monoamine oxidase by imidazoline 2 site‐selective ligands. Ann NY Acad Sci 1999;881:115–117. [DOI] [PubMed] [Google Scholar]
  • 102. Laux G, Volz H‐P, Möller H‐J. Newer and older monoamine oxidase inhibitors. A comparative profile. CNS Drugs 1995;3:145–158. [Google Scholar]
  • 103. Lavie P, Aharon‐Peretz J, Klein F, et al. Sleep quality in geriatric depressed patients: Comparison with elderly demented patients and normal controls and the effects of moclobemide. Dementia 1992;3:360–366. [Google Scholar]
  • 104. Levant B, Moehlenkamp JD, Morgan KA, et al. Modulation of [3H]quinpirole binding in brain by monoamine oxidase inhibitors: Evidence for a potential novel binding site. J Pharmacol Exp Ther 1996;278:145–153. [PubMed] [Google Scholar]
  • 105. Lipper S, Murphy DL, Slater S, et al. Comparative behavioural effects of clorgyline and pargyline in man: A preliminary investigation Psycharmacology 1979;62:123–128. [DOI] [PubMed] [Google Scholar]
  • 106. Livingston MG, Livingston HM. Monoamine oxidase inhibitors. An update of drug interactions. Drug Safety 1996;14:219–227. [DOI] [PubMed] [Google Scholar]
  • 107. Lorenz HP, Harvey J, Wright L. Moclobemide exhibits neuroprotective effects in hypoxic rat brain In: Krieglstein J, Oberpichler H, Eds. Pharmacology of cerebral ischemia. Stuttgart : Wissenschaftliche Verlagsgesellschaft, 1990:477–484. [Google Scholar]
  • 108. Maguire K, Pereira A, Tiller J. Moclobemide pharmacokinetics in depressed patients: Lack of age effect. Hum Psychopharm 1991;6:249–252. [Google Scholar]
  • 109. Magyar K, Szende B, Lengyel J, et al. The neuroprotective and neuronal rescue effects of (‐)‐deprenyl. J Neural Transm 1998;52 (Suppl): 109–123. [DOI] [PubMed] [Google Scholar]
  • 110. Mann JJ, Stanley M. Postmortem monoamine oxidase enzyme kinetics in the frontal cortex of suicide victims and controls. Acta Psychiatr Scand 1984;69:135–139. [DOI] [PubMed] [Google Scholar]
  • 111. Markianos M, Alevizos V, Stefanis C. Plasma sex hormones and urinary biogenic amine metabolites during treatment of male depressed patients with the monoamine oxidase inhibitor moclobemide. Neuroedocrinol Lett 1991;13:49–55. [Google Scholar]
  • 112. Marley E, Wozniak KM. Clinical and experimental aspects of interactions between amine oxidase inhibitors and amine reuptake inhibitors. Psychol Med 1983;13:735–749. [DOI] [PubMed] [Google Scholar]
  • 113. Martin JR, Schaffner R, Rumennik L. Cognitive performance enhancing effects of the reversible MAO inhibitor moclobemide In: Wurtman RJ, Corkin S, Growdon JH, Ritter‐Walker E, Eds. Alzheimer's disease. Cambridge : Center for Brain Sciences and Metabolism Charitable Trust, 1989:689–694. [Google Scholar]
  • 114. Mayersohn M, Guentert TW. Clinical pharmacokinetics of the monoamine oxidase‐A inhibitor moclobemide. Clin Pharmacokinet 1995;29:292–332. [DOI] [PubMed] [Google Scholar]
  • 115. Menkes DB, Aghajanian GK. α1‐Adrenoreceptor‐mediated responses in the lateral geniculate nucleus are enhanced by chronic antidepressant tratment. Eur J Pharmacol 1981;74:27–35. [DOI] [PubMed] [Google Scholar]
  • 116. Möller H‐J, Laux G, Müller WE. Moclobemide. Psychopharmakotherapie 1994;4 (Suppl 2): 3–37. [Google Scholar]
  • 117. Monti JM, Alterwain P, Monti D. The effect of moclobemide on nocturnal sleep of depressed patients. J Affect Disord 1990;20:201–208. [DOI] [PubMed] [Google Scholar]
  • 118. Moreau J‐K, Jenck F, Martin JR, et al. Antidepressant treatment prevents chronic unpredictable mild stress‐induced anhedonia as assessed by ventral tegmentum self‐stimulation behavior in rats. Eur Neuropsychopharmacol 1992;2:43–49. [DOI] [PubMed] [Google Scholar]
  • 119. Moreau J‐K, Jenck F, Martin JR, et al. Effects of moclobemide, a new generation reversible MAO‐A inhibitor, in a novel model of depression. Pharmacopychoarty 1993;26:30–33. [DOI] [PubMed] [Google Scholar]
  • 120. Mori S, Zanardi R, Popoli M, et al. cAMP‐dependent phosphorylation system after short and long‐term administration of moclobemide. J Psychiatr Res 1998;32:111–115. [DOI] [PubMed] [Google Scholar]
  • 121. Morell V. Evidence found for possible “aggression gene. Science 1993;260:1722–1723. [DOI] [PubMed] [Google Scholar]
  • 122. Montkowski A, Barden N, Wotjak C, et al. Long‐term antidepressant tratment reduces behavioural deficits in transgenic mice with impaired glucocorticoid receptor function. J Neuroendocrinol 1995;7:841–845. [DOI] [PubMed] [Google Scholar]
  • 123. Naranjo C. Psychotherapeutic properties of harmala alkaloids In: Efron D, Holmstedt B, Kline N, Eds. Ethnopharmacologic search for psychoactive drugs. New York : Raven Press, 1979:385–396. [Google Scholar]
  • 124. Nestler EJ, Terwilliger RZ, Duman RS. Chronic antidepressant administration alters the subcellular distribution of cyclic AMP dependent protein kinase in rat frontal cortex. J Neurochem 1989;53:1644–1647. [DOI] [PubMed] [Google Scholar]
  • 125. Nestler EJ. Antidepressant treatment in the 21st century. Biol Psychiatry 1998;44:526–533. [DOI] [PubMed] [Google Scholar]
  • 126. Nowakowska E, Chodera A, Kus K, et al. Anxioloytic and memory improving effects of moclobemide. Arzneimittelforschung 1998;48:625–628. [PubMed] [Google Scholar]
  • 127. Olmos G, Gabilondo AM, Miralles A, et al. Chronic treatment with the monoamine oxidase inhibitors clorgyline and pargyline down‐regulates non‐adrenoreceptor [3H]‐idazoxan binding sites in rat brain. Br J Pharmacol 1993;108:597–603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 128. Ordway GA, Farley JT, Dilley GE, et al. Quantitative distribution of monoamine oxidase A in brainstem monoamine nuclei is normal in major depression. Brain Res 1999;847:71–79. [DOI] [PubMed] [Google Scholar]
  • 129. Oreland L, Jossan SS, Hartvig P, et al. Turnover of monoamine oxidase B (MAO‐B) in pig brain by positron emission tomography using 11C‐L‐deprenyl. J Neural Transm 1990;32:55–59. [DOI] [PubMed] [Google Scholar]
  • 130. Pancheri P, Delle‐Chiaie R, Donnini M, et al. Effects of moclobemide on depressive symptoms and cognitive performance in a geriatric population: A controlled comparative study versus imipramine. Clin Neuropharmacol 1994;17 (Suppl 1): S58–S73. [DOI] [PubMed] [Google Scholar]
  • 131. Parini A, Moudanous CG, Pizzinat N, et al. The elusive family of imidazoline binding sites. Trends Pharmacol Sci 1996;17:13–16. [DOI] [PubMed] [Google Scholar]
  • 132. Perez J, Tinelli D, Bianchi E, et al. cAMP binding proteins in the rat cerebral cortex after administration of selective 5‐HT and NE reuptake blockers with antidepressant activity. Neuropsychopharmacology 1991;4:57–64. [PubMed] [Google Scholar]
  • 133. Piletz JE, Halaris A. Involvement of I1‐imidazoline receptors in mood disorders. Ann NY Acad Sci 1995;763:510–519. [DOI] [PubMed] [Google Scholar]
  • 134. Pletscher A, Besendorf H, Bächthold HP, et al. Über pharmakologische Beeinflussung des Zentralnervensystems durch kurzwirksame Monoaminoxydasehemmer aus der Gruppe der Harmala‐Alkaloide. Helv Physiol Acta 1959;17:202–214. [Google Scholar]
  • 135. Pons G, Schoerlin MP, Tam YK, et al. Moclobemide excretion in human breast milk. Br J Clin Pharmacol 1990;29:27–31. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 136. Porsolt RD, Bertin A, Jalfre M. Behavioural despair in mice: A primary screening test for antidepressants. Arch Int Pharmacodyn Ther 1977;229:327–336. [PubMed] [Google Scholar]
  • 137. Porsolt RD. Behavioural despair In: Enna SJ, Malick JB, Richelson E, Eds. Antidepressants: Neurochemical, behavioural and clinical perspectives. New York : Raven Press, 1981:121–139. [Google Scholar]
  • 138. Potter WZ, Murphy DL, Wehr TA, et al. Clorgyline. A new treatment for patients with refractory rapid‐cycling disorder. Arch Gen Psychiatry 1982;39:505–510. [DOI] [PubMed] [Google Scholar]
  • 139. Priest RG, (ed.). The treatment of depression in the 1990s – a focus on moclobemide. Acta Psychiatr Scand 1990;82(Suppl 360): 39–108. [PubMed] [Google Scholar]
  • 140. Raaflaub J, Haefelfinger P, Trautmann KH. Single‐dose pharmacokinetics of the MAO‐inhibitor moclobemide in man. Arzneimitelforschung 1984;34:80–82. [PubMed] [Google Scholar]
  • 141. Radat F, Berlin I, Spreux‐Varoquaux O, et al. Initial monoamine oxidase‐A inhibition by moclobemide does not predict the therapeutic response in patients with major depression. A double blind, randomized study. Psychopharmacology 1996;127:370–376. [DOI] [PubMed] [Google Scholar]
  • 142. Ramaekers JG, Swijgman HF, O'Hanlon JF. Effects of moclobemide and mianserin on highway driving, psychomotor performance and subjective parameters, relative to placebo. Psychopharmacology 1992;106:S62–S67. [DOI] [PubMed] [Google Scholar]
  • 143. Reul JMHM, Stec I, Söder M, et al. Chronic treatment of rats with the antidepressant amitryptiline attenuates the activity of the hypothalamic‐pituitary‐adrenocortical system. Endocrinology 1993;133:312–320. [DOI] [PubMed] [Google Scholar]
  • 144. Reul JMHM, Labeur MS, Grigoriadis DE, et al. Hypothalamic‐pituitary‐adrenocortical axis changes in the rat after long‐term treatment with reversible monoamine oxidase‐A inhibitor moclobemide. Neuroendocrinology 1994;60:509–519. [DOI] [PubMed] [Google Scholar]
  • 145. Robitzek EH, Selikoff IJ. Hydrazine derivates of isonicotinic acid (Rimifon, Marsilid) in the treatment of active progressive caseous‐pneumonic tuberculosis. Am Rev Tuberc 1952;65:402–428. [DOI] [PubMed] [Google Scholar]
  • 146. Rommelspacher H, May T, Salewski B. Harman (1‐methyl‐β‐carboline) is a natural inhibitor of monoamine oxidase A in rat. Eur J Pharmacol 1994;252:51–59. [DOI] [PubMed] [Google Scholar]
  • 147. Saura M, Marti J, Kettler R, et al. Molecular anatomy of MAO‐A and MAO‐B. J Neural Transm 1990;Suppl 32:49–53. [DOI] [PubMed] [Google Scholar]
  • 148. Saura J, Bleuel Z, Ulrich J, et al. Molecular neuroanatomy of human monoamine oxidase A and B revealed by quantitative enzyme radioautography and in situ hybridization histochemistry. Neuroscience 1996;70:755–774. [DOI] [PubMed] [Google Scholar]
  • 149. Schreiber S, Getslev V, Weizman A, et al. The antinociceptive effect of moclobemide in mice is mediated by noradrenergic pathways. Neurosci Lett 1998;253:183–186. [DOI] [PubMed] [Google Scholar]
  • 150. Seiler N, Al‐Therib MJ, Kataoka K. Formation of GAB A from putrescine in the brain offish (Salmo irideus Gibb.). J Neurochem 1973;20:699–708. [DOI] [PubMed] [Google Scholar]
  • 151. Scheinin M, Koulu M, Vakkuri O, et al. Moclobemide, an inhibitor of MAO‐A, does not increase daytime plasma melatonin levels in normal humans. Prog Neuropsychopharmacol Biol Psychiatry 1990;14:73–82. [DOI] [PubMed] [Google Scholar]
  • 152. Scherschlicht R, Polc P, Schneeberger J, et al. Selective suppression of rapid eye movement sleep (REMs) in rats by typical and atypical antidepressants In: Costa E, Racagni G, Eds. Typical and atypical antidepressants. New York : Raven Press, 1982:359–364. [PubMed] [Google Scholar]
  • 153. Schoerlin M‐P, 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. [DOI] [PubMed] [Google Scholar]
  • 154. Schoerlin M‐P, Da Prada M. Species‐specific biotransformation of moclobemide: A comparative study in rats and humans. Acta Psychiatr Scand 1990;82 (Suppl 360): 108–110. [DOI] [PubMed] [Google Scholar]
  • 155. Schoerlin M‐P, 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;30:272–284. [DOI] [PubMed] [Google Scholar]
  • 156. Sherif F, Marcusson J, Oreland L. Brain gamma‐aminobutyrate transaminase and monoamine oxidase activities in suicide victims. Eur Arch Psych Clin Neurosci 241:139–144. [DOI] [PubMed] [Google Scholar]
  • 157. Shih JC. Molecular basis of human MAO A and B. Neuropsychopharmacology 1991;4:1–7. [PubMed] [Google Scholar]
  • 158. Silver H, Youdim MBH. MAO‐A and MAO‐B activities in rat striatum, frontal cortex and liver are unaltered after long‐term treatment with fluvoxamine and desipramine. Eur Neuropsychopharmacol 2000;10:125–128. [DOI] [PubMed] [Google Scholar]
  • 159. Simpson GM, Gratz SS. Comparison of the pressure effect of tyramine after treatment with phenelzine and moclobemide in healthy male volunteers. Clin Pharmacol Ther 1992;52:286–291. [DOI] [PubMed] [Google Scholar]
  • 160. Smith GAM, Brett CL, Church J. Effects of noradrenaline on intracellular pH in acutely dissociated adult rat hippocampal neurons. J Physiol 1998;512:487–505. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 161. Stabl M, Bizière W, Schmid‐Burgk W, et al. Review of comparative clinical trials. Moclobemide vs. tricyclic antidepressants and vs. placebo in depressive states. J Neural Transm 1989;Suppl 28:77–89. [PubMed] [Google Scholar]
  • 162. Steckler T, Rammes G, Sauvage M, et al. Effects of the monoamine oxidase A inhibitor moclobemide on hippocampal plasticity in GR‐impaired transgenic mice. J Psychiat Res 2001;35:29–42. [DOI] [PubMed] [Google Scholar]
  • 163. Steiger A, Holsboer F, Benkert O. Long term studies on the effect of tricyclic antidepressants and selective MAO‐A inhibitors on sleep, nocturnal penile tumescence and hormonal secretion in normal controls In: Koella WP, Ed. Sleep. Stuttgart : Verlag, 1988:335–337. [Google Scholar]
  • 164. Stern G. Neuroprotection by selegiline and other MAO inhibitors. J Neural Transm 1998;52 (Suppl): 99–107. [DOI] [PubMed] [Google Scholar]
  • 165. 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): 94–97. [DOI] [PubMed] [Google Scholar]
  • 166. Strolin‐Benedetti M, Dostert P. Monoamine oxidase, brain aging and degenerative diseases. Biochem Pharmacol 1989;38:555–561. [DOI] [PubMed] [Google Scholar]
  • 167. Strolin‐Benedetti M, Kettler R, Marrai P, et al. The effects of lifelong treatment with MAO inhibitors on amino acid levels in rat brain. J Neural Transm 1990;2:239–248. [DOI] [PubMed] [Google Scholar]
  • 168. Takahashi K‐I, Copenhagen DR. Modulation of neuronal function by intracellular pH. Neurosci Res 1996;24:109–116. [DOI] [PubMed] [Google Scholar]
  • 169. Tiller JWG, Bouwer C, Behnke K. Moclobemide for anxiety disorders: A focus on moclobemide for panic disorder. Int Clin Psychopharmacol 1997;12 (Suppl 6): S27–S30. [PubMed] [Google Scholar]
  • 170. Trendelenburg U, Langeloh A, Bönisch H. Mechanism of indirectly acting sympathomimetic amines. Blood Vessels 1987;24:261–270. [DOI] [PubMed] [Google Scholar]
  • 171. Trudeau LE, Parpura V, Hay don PG. Activation of neurotransmitter release in hippocampal nerve terminals during recovery from intracellular acidification. J Neurophysiol 1999;81:2627–2635. [DOI] [PubMed] [Google Scholar]
  • 172. Vetulani J, Sulser F. Action of various antidepressant treatments reduces reactivity of noradrenergic cyclic AMP‐generating system in limbic forebrain. Nature 1975;257:495–496. [DOI] [PubMed] [Google Scholar]
  • 173. Vignes M, Blanc E, Guiramand J, et al. A modulation of glutamate‐induced phosphoinositide breakdown by intracellular pH changes. Neuropharmacology 1996;45:1595–1604. [DOI] [PubMed] [Google Scholar]
  • 174. Von Korff RW. Monoamine oxidase: unanswered questions In: Singer TP, von Korff RW, Murphy DL, Eds. Monoamine oxidase: Structure, function and altered functions. New York : Academic Press, 1979:1–7. [Google Scholar]
  • 175. Walaas, Greengard P. Protein phosphorylation and neuronal function. Pharmacol Rev 1991;43:299–334. [PubMed] [Google Scholar]
  • 176. Waldmeier PC. Amine oxidases and their endogenous substrates (with special reference to monoamine oxidase and the brain). J Neural Transm 1987;23 (Suppl): 55–72. [DOI] [PubMed] [Google Scholar]
  • 177. Wesnes KA, Simpson PM, Christmas L, et al. The effects of moclobemide on cognition. J Neural Transm 1989;28 (Suppl): 91–102. [PubMed] [Google Scholar]
  • 178. Westlund KN, Denny RM, Kochersberger LM, et al. Distinct monoamine oxidase A and B populations in primate brain. Science 1985;230:181–183. [DOI] [PubMed] [Google Scholar]
  • 179. Willner P. Animal models as simulations of depression. TIPS 1991;12:131–136. [DOI] [PubMed] [Google Scholar]
  • 180. Youdim MBH, Finberg JPM, Tipton KF. Monoamine oxidase In: Trendelenburg U, Weiner N, Eds. CatecholaminesI. Berlin : Springer, 1988:119–192. [Google Scholar]
  • 181. Young JD, Cohen DJ, Waldo MD, et al. Platelet monoamine oxidase activity in children and adolescents with psychiatric disorders. Schizophren Bull 1980;6:324–333. [DOI] [PubMed] [Google Scholar]

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