Chronopharmacological study of neuroleptics. II. Circadian susceptibility rhythm to chlorpromazine

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 fluctua...

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Bibliographic Details
Published inPsychopharmacology Vol. 58; no. 1; p. 49
Main Authors Nagayama, H, Takagi, A, Sakurai, Y, Nishiwaki, K, Takahashi, R
Format Journal Article
LanguageEnglish
Published Germany 15.06.1978
Subjects
Animals
Brain - metabolism
Chlorpromazine - metabolism
Chlorpromazine - pharmacology
Chlorpromazine - toxicity
Circadian Rhythm
Dealkylation
Hypnotics and Sedatives
Male
Rats
Time Factors
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Summary: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 addidtion, daily fluctuation due to time of administration was noted in lethality.
ISSN:0033-3158
1432-2072
DOI:10.1007/BF00426789