Abstract
The circadian fluctuation of sedative effect of haloperidol was experimentally studied, as part of the series of investigations on circadian fluctuation of the effect of neuroleptics. Haloperidol of various doses was administered at various times during the day to rats which had been housed with strictly controlled lighting schedule and room temperature. It was shown that sedative effect of haloperidol was significantly affected by the time of day of administration, that is, there is a circadian fluctuation, and also that the variation pattern changed with different doses of this drug. In order to study the mechanism underlying this circadian fluctuation, time course changes in plasma and brain concentrations of the drug were measured. No significant difference in the concentrations was observed among the different times of administration. It was thus suggested that the circadian fluctuation of sedative effect of haloperidol might be due to the circadian rhythm of brain susceptibility to the drug. Antiapomorphine action of haloperidol was then examined using stereotyped behavior of the rat as an index. The result indicated the presence of the circadian fluctuation of antiapomorphine action which was in a pattern similar to the variation of the sedative effect of haloperidol. Based on the experimental results thus obtained, the generating mechanism for the circadian fluctuation of sedative effect of haloperidol was discussed.
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Nagayama, H., Takagi, A., Sakurai, Y. et al. Chronopharmacological study of neuroleptics. Psychopharmacology 63, 131–135 (1979). https://doi.org/10.1007/BF00429690
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DOI: https://doi.org/10.1007/BF00429690