CHRONOPHARMACOLOGICAL STUDY OF KE-SI-TO COMPONENTS IN MICE

influence of dosing time on pharmacological effects and toxicity of KE -SITO (KST) components, as well as the role of each component in the c ircadian rhythms of KST, was investigated in ICR male mice under an LD (12:12) cycle. The mice given Cinnamomi Cortex (258 mg/kg, i.p.) or P aeoniae Radix (258 mg/kg, i.p.) showed a significant circadian rhythm in the time spent on the hot plate with the shortest latency at 0900 a nd the longest one at 0100 (p<0.01, respectively). The mice given Cinn amomi Cortex or Glycyrrhizae Radix (129 mg/kg, i.p.) showed a signific ant circadian rhythm with the lowest rectal temperature (RT) at 1700 a nd the highest one at 0500 (p<0.01, respectively). Cinnamomi Cortex (8 50 mg/kg, i.p.)- or Glycyrrhizae Radix (2500 mg/kg, i.p.)-induced toxi city showed a significant circadian rhythm with the highest mortality at 1700 and the lowest one at 0500 (p<0.05, respectively). The rhythmi c patterns of the drug-induced analgesia, hypothermia and toxicity res embled the overall rhythms occurring after KST (1000 or 6000 mg/kg, i. p.) injection. These results suggest that the circadian rhythms in act ions of Cinnamomi Cortex, Paeoniae Radix and Glycyrrhizae Radix are ma inly responsible for the rhythm in the effects and toxicity of KST.