Abstract
The effect of pimozide, a potent and specific blocker of central dopaminergic transmission, upon the sleep of man was studied in six healthy volunteers. Given at doses of 1 and 4 mg, which have clear central effects in humans, pimozide produced only minor changes in the EEG patterns of sleep. At these doses a slight and non-significant decrease in phase I sleep was observed, while phases W, II, III, IV and REM were not modified. No differences were noted between drug or post-treatment and control nights in total NREM sleep, total REM sleep, number of episodes of REM or total number of eye movements. An increase in REM sleep in the first third of the second pimozide night and an increase in the duration of the first REM period in the first drug night were the only statistically significant findings. If one accepts that central effects seen in man after pimozide given in conditions similar to those of this study are due to dopaminergic blockade, our results tend to suggest that dopamine is, at most, of rather minor importance in the physiology of sleep in man.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Andén, N.-E., Butcher, S. G., Corrodi, H., Fuxe, K., Ungerstedt, U.: Receptor activity and turnover of dopamine and noradrenaline after neuroleptics. Europ. J. Pharmacol. 11, 303–314 (1970)
Brodie, B. B., Comer, M. S., Costa, E., Dlabac, A.: The role of brain serotonin in the mechanism of the central action of reserpine. J. Pharmacol. exp. Ther. 152, 340–349 (1966)
Dement, W., Kleitman, N.: Cyclic variations in EEG during sleep and their relations to eye movements, body motility and dreaming. Electroenceph. clin. Neurophysiol. 9, 673–690 (1957)
Dunleavy, D, L. F., Brezinova, V., Oswald, I., MacLean, A. W., Tinker, M.: Changes during weeks in effects of tricyclic drugs on the human sleeping brain. Brit. J. Psychiat. 120, 663–672 (1972)
George, R., Haslett, W. L., Jenden, D. J.: A cholinergic mechanism in the brainstem reticular formation: induction of paradoxical sleep. Int. J. Neuropharmacol. 3, 541–552 (1964)
Hartmann, E., Zwilling, G. R., Koski, S.: The effects of pimozide on sleep in the rat. Paper presented at the Meeting of the Association for the Psychophysiological Study of Sleep, San Diego, California (1973)
Hoffman, J., Domino, E. F.: Comparative effects of reserpine on the sleep cycle of man and cat. J. Pharmacol. exp. Ther. 170, 190–198 (1969)
Janke, W., Debus, G.: Double-blind psychometric evaluation of pimozide and haloperidol versus placebo in emotionally labile volunteers under two different work load conditions. Pharmakopsychiat. 1, 34–51 (1972)
Janssen, A. J., Niemegeers, C. J. E., Schellekens, K. H. L., Dresse, A., Lenaerts, F. M., Pinchard, A., Schaper, W. K. A., Van Nueten, J. M., Verbruggen, F. J.: Pimozide, a chemically novel, highly potent and orally long-acting neuroleptic drug. Arzneimittel-Forsch. 18, 261–287 (1968)
Jasper, H. H.: The ten twenty electrode system of the International Federation. Electroenceph. clin. Neurophysiol. 10, 371–375 (1958)
Jouvet, M.: Etude electrophysiologique et neuropharmacologique des états de sommeil. Actualités Pharmacol. 18, 109–173 (1965)
Jouvet, M.: Biogenic amines and the states of sleep. Science 163, 32–41 (1969)
Jouvet, M., Bobillier, P., Pujol, J. F., Renault, J.: Effets des lésions du système du raphé sur le sommeil et la sérotonine cérébrale. C. R. Soc. Biol. (Paris) 160, 2343–2346 (1966)
Kales, A., Ansel, R. D., Markham, C. H., Scharf, M. B., Tan, T.: Sleep in patients with Parkinson's disease and normal subjects prior to and following levodopa administration. Clin. Pharmacol. Ther. 12, 397–406 (1971)
Lewis, S. A., Evans, J. I.: Dose effects of chlorpromazine on human sleep. Psychopharmacologia (Berl.) 14, 342–348 (1969)
Sagalés, T., Erill, S., Domino, E. F.: Differential effects of scopolamine and chlorpromazine on REM and NREM sleep in normal male subjects. Clin. Pharmacol. Ther. 10, 522–529 (1969)
Stern, M., Roffwarg, H., Duvoisin, R.: The parkinsonian tremorinsleep. J. nerv. ment. Dis. 147, 202–210 (1968)
Williams, R. L., Agnew, H. W., Webb, W. B.: Sleep patterns in young adults: An EEG study. Electroenceph. clin. Neurophysiol. 17, 376–381 (1964)
Wyatt, R. J., Chase, T. N., Kupfer, D. J., Scott, J., Snyder, F., Sjoerdsma, A., Engelman, K.: Brain catecholamines and human sleep. Nature (Lond.) 233, 63–65 (1971a)
Wyatt, R. J., Chase, T. N., Scott, J., Snyder, F., Engelman, K.: Effect of l-Dopa on the sleep of man. Nature (Lond.) 228, 999–1001 (1970)
Wyatt, R. J., Engelman, K., Kupfer, D. J., Scott, J., Sjoerdsma, A., Snyder, F.: Effects of para-chlorophenylalanine on sleep in man. Electroenceph. clin. Neurophysiol. 27, 529–532 (1969)
Wyatt, R. J., Zarcone, V., Engelman, K., Dement, W. C., Snyder, F., Sjoerdsma, A.: Effects of 5-hydroxytryptophan on the sleep of normal human subjects. Electroenceph. clin. Neurophysiol. 30, 505–509 (1971b)
Yamamoto, K., Domino, E. F.: Cholinergic agonist-antagonist interactions on neocortical and limbic EEG activation. Int. J. Neuropharmacol. 6, 357–373 (1967)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Sagalés, T., Erill, S. Effects of central dopaminergic blockade with pimozide upon the EEG stages of sleep in man. Psychopharmacologia 41, 53–56 (1975). https://doi.org/10.1007/BF00421306
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00421306