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Circadian susceptibility rhythm to neuroleptics: Tetrabenazine

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Abstract

In order to clarify the influences of situational factors on the effects of psychotropic drugs, the sedative effects of tetrabenazine after injection at various times of the day were studied. When 50 mg/kg body weight of tetrabenazine was injected into rats at eight different times of the day (07∶30–19∶30 dark, 19∶30–07∶30 light), a circadian rhythm of sedative effect was observed with a peak sedative time of 1490 min at 10∶30 and a nadir of 736 min at 07∶30. With 10 mg/kg body weight of tetrabenazine a similar circadian rhythm of sedative effect was observed. This rhythm did not appear to be due to differences of metabolism of tetrabenazine in the tissues, but rather to be closely related to daily fluctuation of serotonin synthesis and release in the brain.

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References

  • Aprison, M. H., Takahashi, R., Tachiki, K. H.: Hypersensitive serotonergic receptors involved in clinical depression—a theory. In: Neuropharmacology and behavior, B. Haber and M. Aprison, eds. New York: Plenum (in press) 1977

    Google Scholar 

  • Bobillier, P., Mouret, J. R.: The alterations of the diurnal variations of brain tryptophan, biogenic amines and 5-hydroxyindole acetic acid in the rat under limited time feeding. Int. J. Neurosci. 2, 271–282 (1971)

    Google Scholar 

  • Chan, O., Welbster, R. A.: Effect of tetrabenazine and α-methylm-tyrosine on exploratory activity and brain catecholamines in rats. Br. J. Pharmacol. 41, 691–699 (1971)

    Google Scholar 

  • Davis, W. H.: Day-night periodicity in pentobarbital response of mice and the influences of socio-psychological conditions. Experimentia 18, 235–237 (1962)

    Google Scholar 

  • Dimascio, A., Shader, R. I.: Drug administration schedules. Am. J. Psychiatry 126, 769–801 (1969)

    Google Scholar 

  • Emlen, S. T., Kem, W.: Activity rhythm in peromyscus: its influence on rats of recovery from nembutal. Science 142, 1682–1683 (1963)

    Google Scholar 

  • Héry, F., Rouer, E., Glowinski, J.: Daily variations of serotonin metabolism in the rat brain. Brain Res. 43, 445–465 (1972)

    Google Scholar 

  • Honingfeld, G.: Non specific factors in treatment. I. Review of placebo reactions and placebo reactors. Dis. Nerv. Syst. 25, 145–156 (1964a)

    Google Scholar 

  • Honingfeld, G.: Non specific factors in treatment. II. Review of social-psychological factors. Dis. Nerv. Syst. 25, 225–239 (1964b)

    Google Scholar 

  • Jori, A., Salle, E., Santini, V.: Daily rhythmic variation and liver drug metabolism in rats. Biochem. Pharmacol. 20, 2965–2969 (1971)

    Google Scholar 

  • 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

    Google Scholar 

  • Nair, V.: Circadian rhythm in drug action; a pharmacologic, biochemical and electromicroscopic study. In: Chronobiology, L. E. Scheving, F. Halberg, and J. E. Pauly, eds., pp. 182–186. Tokyo: Igaku Shoin 1974

    Google Scholar 

  • Nair, V., Casper, R.: The influence of light on daily rhythm in hepatic drug metabolizing enzymes in rat. Life Sci. 8, 1219–1298 (1969)

    Google Scholar 

  • Nakamura, E., Tateishi, T., Nagayma, H., Sakurai, Y., Takahashi, R.: Biochemical studies on tetrabenazine model of depression. Annual Report of the Pharmacopsychiatry Research Foundation 4, 49–54 (1973)

    Google Scholar 

  • Quay, W. B.: Circadian rhythm in rat pineal serotonin and its modifications by estrous cycle and photoperiod. Gen. Comp. Endocrinol. 3, 473–479 (1963)

    Google Scholar 

  • Quay, W. B.: Regional and circadian differences in cerebral cortical serotonin concentrations. Life Sci. 4, 379–384 (1965)

    Google Scholar 

  • Quay, W. B.: Differences in circadian rhythms in 5-hydroxytryptamine according to brain regions. Am. J. Physiol. 215, 1448–1453 (1968)

    Google Scholar 

  • Quinn, G. P., Shore, D. A., Brodie, B. B.: Biochemical and pharmacological studies on Ro-1-9569 (tetrabenazine), a non-indole tranquilizing agent with reserpine-like effects. J. Pharm. Exp. Ther. 127, 103–109 (1959)

    Google Scholar 

  • Radzialowski, F. M., Bousquet, W. F.: Daily rhythmic variations in hepatic drug metabolism in the rat and mouse. J. Pharm. Exp. Ther. 163, 229–238 (1968)

    Google Scholar 

  • Reinberg, A.: Chronopharmacology. Biochemical aspects of circadian rhythms, J. N. Mills, ed., pp. 121–152. London: Plenum 1973

    Google Scholar 

  • Rickels, K.: Non-specific factors in drug therapy. Springfield: C. C. Thomas 1968

    Google Scholar 

  • Roberts, P., Turnbull, M. J., Winterburn, A.: Diurnal variation sensitivity to and metabolism of barbiturate in the rat: lack of correlation between in vivo and in vitro findings. Eur. J. Pharmacol. 12, 375–377 (1970)

    Google Scholar 

  • Scheving, L. E., Harrison, W. H., Gordon, P., Pauly, J. E.: Daily fluctuation (circadian and ultradian) in biogenic amines of the rat brain. Am. J. Physiol. 214, 166–173 (1968a)

    Google Scholar 

  • Scheving, L. E., Vendral, D. F., Pauly, J. E.: A circadian susceptibility rhythm in rat to pentobarbital sodium. Anat. Rec. 160, 7410749 (1968b)

    Google Scholar 

  • Simon, M. L., George, R.: Diurnal variations in plasma corticosterone and growth hormone as correlated with regional variations in norepinephrine, dopamine and serotonin content of rat brain. Neuroendocrinology 17, 125–138 (1975)

    Google Scholar 

  • Tachiki, K. H., Takagi, A., Tateishi, T., Kido, A., Nishiwaki, K., Nakamura, E., Nagayama, H., Takahashi, R.: Animal model of depression. III. Mechanism of action of tetrabenazine. Biol. Psychiatry (in press, 1977)

  • Tateishi, T., Tachiki, K., Nakamura, E., Takagi, A., Nagayama, H., Sakurai, Y., Takahashi, R.: Behavioral sedation in animals and associated biochemical changes—study of a model of depression induced by tetrabenazine in rats. Bulletin of Neuroinformation Laboratory, Nagasaki University 2, 96–105 (1975)

    Google Scholar 

  • Utena, H.: Factors influencing the effects of psychotropic drugs; personal and situational responses. Seitai no Kagaku 14, 28–35 (1963)

    Google Scholar 

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Nagayama, H., Takagi, A., Tateishi, T. et al. Circadian susceptibility rhythm to neuroleptics: Tetrabenazine. Psychopharmacology 55, 61–66 (1977). https://doi.org/10.1007/BF00432818

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  • DOI: https://doi.org/10.1007/BF00432818

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