Abstract
In order to study differences in the effect of the neuroleptics due to time of administration, rats were administered chlorpromazine (CPZ) in a variety of combinations of dose and time and the sedation period was measured. There was daily fluctuation in the sedative effect and the pattern of fluctuation differed according to dosage. A similar study under the condition of reversed light and dark gave a reversed curve of the daily fluctuation, showing that the rhythm of light and dark controls the fluctuation externally. In an attempt to elucidate the mechanism of these phenomena, CPZ was administered at two different times, between which there was a significant difference in the sedation period, and time-course changes in plasma and brain concentration of the drug and its metabolites were measured. No difference was found. These results are interpreted as indicating that the phenomena could arise at the level of amine-receptor activity in the brain. In addition, daily fluctuation due to time of administration was noted in lethality.
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., Rubenson, A., Fuxe, K., Hökfelt, T.: Evidence for dopamine receptor stimulation by apomorphine. J. Pharm. Pharmacol. 19, 627–629 (1967)
Curry, S. H.: Determination of nanogram quantities of chlorpromazine and some of its metabolism in plasma using gas-liquid chromatography with an electron capture detector. Anal. Chem. 40, 1251–1255 (1968)
Davis, W. M.: Day-night periodicity in pentobarbital response of mice and the influence of socio-psychological conditions. Experientia 18, 235–237 (1962)
Davies, J. A., Redfern, P. H.: The effects of hallucinogenic drugs on maze exploration in the rat over a 24 hour period. Br. J. Pharmacol. 49, 121–127 (1973)
Emlen, S. T., Kem, W.: Activity rhythm in peromyscus: its influence on rates of recovery from nembutal. Science 142, 1682–1683 (1963)
Ernst, A. M.: Mode of action of apomorphine and dexamphetamine on gnawing compulsion in rats. Psychopharmacologia (Berl.) 10, 316–323 (1967)
Evans, H. L., Ghiselli, W. B., Patton, R. A.: Diurnal rhythm in behavioral effects of methamphetamine, P-chloromethamphetamine and scopolamine. J. Pharmacol. Exp. Ther. 186, 10–17 (1973)
Focan, C.: Circadian rhythm and chemotherapy for cancer. Lancet 1976II, 638–639
Friedman, A. H., Walker, C. A.: Amines, blood histamine and glucose levels in relationship to circadian changes in sleep induced by pentobarbitone sodium. J. Physiol. 202, 133–146 (1969)
Halberg, F., Haus, E., Cardoso, S. S., Scheving, L. E., Kühl, J. F. W., Shiotsuka, R., Rosene, G., Pauly, J. E., Runge, W., Spalding, J. F., Lee, J. K., Good, R. A.: Toward a chronotherapy of neoplasia: tolerance of treatment depends upon host rhythm. Experientia 29, 909–1044 (1973)
Holcslaw, T. L., Miya, T. S., Bousquet, W. S.: Circadian rhythms in drug action and drug metabolism in the mouse. J. Pharmacol. Exp. Ther. 195, 320–322 (1975)
Moore Ede, M. C., Burr, R. G.: Circadian rhythm of therapeutic effectiveness of oxymetholone in paraplegic patients. Clin. Pharmacol. Ther. 14, 448–454 (1973)
Müller, O.: Circadian rhythmicity in response to barbiturates. In: Chronobiology, L. E. Scheving, F. Halberg, and J. E. Pauly, eds., pp. 187–190. Tokyo: Igaku Shoin 1974
Nagayama, H., Takagi, A., Tateishi, T., Takahashi, R.: Circadian susceptibility rhythm to neuroloptics: tetrabenazine. Psychopharmacology 55, 61–66 (1977)
Nair, V., Casper, R.: The influence of light on daily rhythm in hepatic drug metabolizing enzymes in rat. Life Sci. 8, 1291–1298 (1969)
Nair, V.: Circadian rhythm in drug action: a pharmacologic, biochemical, and electronmicroscopic study. In: Chronobiology, L. E. Scheving, F. Halberg, and J. E. Pauly, eds., pp. 182–186. Tokyo: Igaku Shoin 1974
Reinberg, A., Sidi, E.: Circadian changes in the inhibitory effects of an antihistaminic drug in man. J. Invest. Dermatol. 46, 415–419 (1966)
Romero, J. A., Zatz, M., Kebabian, J. W., Axelrod, J.: Circadian cycles in binding of 3H-alprenolol to β-adrenergic receptors sites in rat pineal. Nature 258, 435–436 (1975)
Scheving, L. E., Vedral, D. F., Pauly, J. E.: A circadian susceptibility rhythm in rats to pentobarbital sodium. Anat. Rec. 160, 741–749 (1968)
Smolensky, M. H., Reinberg, A.: The chronotherapy of corticosteroids: practical application of chronobiologic findings of nursing. Nurs. Clin. North. Am. 11, 609–619 (1976)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Nagayama, H., Takagi, A., Sakurai, Y. et al. Chronopharmacological study of neuroleptics. Psychopharmacology 58, 49–53 (1978). https://doi.org/10.1007/BF00426789
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00426789