Psychopharmacology

, Volume 78, Issue 2, pp 137–140

REM sleep suppression induced by selective monoamine oxidase inhibitors

  • Robert M. Cohen
  • David Pickar
  • Debra Garnett
  • Steven Lipper
  • J. Christian Gillin
  • Dennis L. Murphy
Original Investigations

Abstract

The effects of 4 weeks of treatment with the selective monoamine oxidase (MAO) inhibiting antidepressants clorgyline and pargyline on the sleep of affectively disordered patients were studied. Both inhibitors resulted in near total suppression of REM sleep, a decrease in total sleep time, and an increase in the percent of stage 2 sleep. Clorgyline also increased awake time and decreased total recording period and sleep latency. In general, changes were greater for clorgyline than for pargyline and were about 50% slower to return to baseline after clorgyline compared to pargyline discontinuation. The results were consistent with the hypothesis that selective inhibition of the MAO type A, as produced by clorgyline, is sufficient to induce marked sleep changes. MAO inhibitor-induced receptor changes are proposed to account for the time course of the REM suppression and the REM rebound observed upon withdrawal.

Key words

Clorgyline Pargyline Receptors 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Akindele MO, Evans JI, Oswald I (1970) Monoamine oxidase inhibitors, sleep and mood. Electroencephalogr Clin Neurophysiol 29:47–56Google Scholar
  2. Campbell IC, Robinson DS, Lovenberg W, Murphy DL (1979a) The effects of chronic regimens of clorgyline and pargyline on monoamine metabolism in rat brain. J Neurochem 32:49–55Google Scholar
  3. Campbell IC, Murphy DL, Gallager DW, Tallman JF, Marshall EF (1979b) Neurotransmitter-related adaptation in the central nervous system following chronic monoamine oxidase inhibition. In: Singer TP, Von Korff RW, Murphy DL (eds) Monoamine oxidase: Structure, function and altered functions. Academic, New York, pp 517–530Google Scholar
  4. Cohen RM, Campbell IC, Dauphin M, Tallman JF, Murphy DL (1982) Changes in alpha- and beta-receptor densities in rat brain as a result of treatment with monoamine oxidase-inhibiting antidepressants. Neuropharmacology 21:293–298Google Scholar
  5. Endicott J, Spitzer RL (1978) A diagnostic interview: The schedule for affective disorders and schizophrenia. Arch Gen Psychiatry 35:837–844Google Scholar
  6. Gillin JC, Wyatt RJ, Fram D, Snyder F (1978) The relationship between changes in REM sleep and clinical improvement in depressed patients treated with amitriptyline. Psychopharmacology 59:267–272Google Scholar
  7. Hawkins DR, Mendels T (1966) Sleep disturbance in depressive syndromes. Am J Psychiatry 123:682–689Google Scholar
  8. Hill SY, Reyes RB, Kupfer DJ (1980) Imipramine and REM sleep: Cholinergic mediation in animals. Psychopharmacology 69:5–9Google Scholar
  9. Jouvet M (1972) The role of monoamines and acetylcholine containing neurons in the regulation of the sleep-waking cycle. Ergeb Physiol 64:166–307Google Scholar
  10. Karczmer AG, Longo VG, Scotti de Carolis A (1970) A pharmacological model of paradoxical sleep: the role of cholinergic and monoamine systems. Physiol Behav 5:175–182Google Scholar
  11. Kupfer DJ, Foster FG, Reich L (1975) EEG sleep changes and predictors in depression. Am J Psychiatry 133:622–626Google Scholar
  12. Kupfer DJ, Hanin I, Spiker DG, Neil T, Goble P (1979) EEG sleep and tricyclic plasma levels in primary depression. Commun Psychopharmacol 3:73–80Google Scholar
  13. Lipper S, Murphy DL, Slater S, Buchsbaum MS (1979) Comparative behavioral effects of clorgyline and pargyline in man: A preliminary evaluation. Psychopharmacology 62:123–128Google Scholar
  14. Mendels J, Chernik DA (1975) Sleep changes and affective illness. In: Elack FF, Dragh SC (eds) The nature and treatment of depression. Wiley, New York, pp 309–333Google Scholar
  15. Mendelson WB, Gillin JC, Wyatt RJ (1977) Human sleep and its disorders. Plenum, New York, pp 21–62Google Scholar
  16. Morgane PJ, Stern WC (1974) Chemical anatomy of brain circuits in relation to sleep and wakefulness. Adv Sleep Res 1:1–131Google Scholar
  17. Murphy DL (1978) Substrate-selective monoamine oxidases: Inhibitor, tissue, species and functional differences. Biochem Pharmacol 27:1889–1893Google Scholar
  18. Murphy DL, Lipper S, Slater S, Shilling D (1979) Selectivity of clorgyline and pargyline as inhibitors of monoamine oxidases A and B in vivo in man. Psychopharmacology 62:129–132Google Scholar
  19. Murphy DL, Lipper S, Pickar D, Jimerson D, Cohen RM, Garrick NA, Alterman IS, Campbell IC (1981) Selective inhibition of monoamine oxidase type A: Clinical antidepressant effects and metabolic changes in man. In: Youdim MBH, Paykel ES (eds) Monoamine oxidase inhibitors: The state of the art. Wiley, New York, pp 189–205Google Scholar
  20. Peroutka SJ, Snyder SH (1980) Long-term antidepressant treatment decreases spiroperidol-labeled serotonin receptor binding. Science 210:88–90Google Scholar
  21. Rechtschaffen A, Kales A (eds) (1968) A manual of standardized terminology, techniques, and scoring system for sleep stages of human subjects. National Institutes of Health, BethesdaGoogle Scholar
  22. Savage DD, Mendels J, Frazer A (1980) Monoamine oxidase inhibitors and serotonin uptake inhibitors: Differential effects on 3H-serotonin binding sites in rat brain. J Pharmacol Exp Ther 212:259–263Google Scholar
  23. Sellinger-Barnette MM, Mendels J, Frazer A (1980) The effect of psychoactive drugs on beta-adrenergic receptor binding sites in rat brain. Neuropharmacology 19:447–454Google Scholar
  24. Siever LJ, Cohen RM, Murphy DL (1981) Antidepressants and α2-autoreceptor desensitization. Am J Psychiatry 138:681–682Google Scholar
  25. Sitaram N, Wyatt RJ, Dawson S, Gillin JC (1976) REM sleep induction by physostigmine infusion during sleep. Science 191:1281–1283Google Scholar
  26. Spitzer RL, Endicott J, Robins E (1978) Research diagnostic criteria: Rationale and reliability. Arch Gen Psychiatry 35:773–782Google Scholar
  27. Vogel GW (1975) A review of REM sleep deprivation. Arch Gen Psychiatry 32:749–761Google Scholar
  28. Wyatt RJ, Kupfer DJ, Scott J, Robinson DS, Snyder F (1969) Longitudinal studies of the effect of monoamine oxidase inhibitors on sleep in man. Psychopharmacologia 15:233–236Google Scholar
  29. Wyatt RJ, Chase TN, Kupfer DJ, Scott J, Snyder F, Sjoerdsma A, Engel K (1971) Brain catecholamines and human sleep. Nature 233:63–65Google Scholar

Copyright information

© Springer-Verlag 1982

Authors and Affiliations

  • Robert M. Cohen
    • 1
  • David Pickar
    • 1
  • Debra Garnett
    • 1
  • Steven Lipper
    • 2
  • J. Christian Gillin
    • 1
  • Dennis L. Murphy
    • 1
  1. 1.National Institute of Mental HealthBethesdaUSA
  2. 2.Veterans Administration HospitalAnn ArborUSA

Personalised recommendations