2002 Fiscal Year Final Research Report Summary
Development of Chronotherapy Based on Clock Genes
| Project/Area Number |
13672391
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | Kyushu University |
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Principal Investigator |
OHDO Shigehiro Graduate School of Pharmaceutical Sciences Associate Professor, 大学院・薬学研究院, 助教授 (00223884)
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| Co-Investigator(Kenkyū-buntansha) |
HIGUCHI Shun Graduate School of Pharmaceutical Sciences Professor, 大学院・薬学研究院, 教授 (40218699)
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| Project Period (FY) |
2001 – 2002
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| Keywords | Biological Rhythm / Clock genes / Suprachiasmatic Nuclei / Chronopharmacology / Chronopharmacokinetics |
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| Research Abstract |
Mammal ians circadian pacemaker resides in the paired suprachiasmatic nuclei (SCN). Clock genes are the genes that control the circadian rhythms in physiology and behavior. The effectiveness and toxicity of many drugs vary depending on dosing time associated with 24-hr rhythms of biochemical, physiological and behavioral processes under the control of circadian clock. However, many drugs are still given without regard to the time of day. Identification of a rhythmic marker for selecting dosing time will lead to improved progress and diffusion of chronopharmacotherapy. In the present study, the following points were clarified. To monitor the rhythmic marker may be useful to choose the most appropriate time of day for administration of drugs that may increase their therapeutic effects and/or reduce their side effects. Also, we showed the disruptive effect of interferon on the rhythm of locomotor activity, body temperature and clock genes mRNA expression in the periphery and SCN. The alteration of the clock function, a new concept of adverse effects, can be overcome by devising a dosing schedule that minimizes adverse drug effects on clock function. Furthermore, to produce new rhythmicity by manipulating the conditions of living organs by using rhythmic administration of altered feeding schedules or several drugs maylead to the new concept of chronopharmacotherapy.
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Research Products
(10 results)
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[Publications] Wang, D.S., Ohdo, S., Koyanagi, S., Takane, H., Aramaki, H., Yukawa, E., Higuchi, S.: "Effect of dosing schedule on pharmacokinetics of alpha interferon and anti-alpha interferon neutralizing antibody in mice."Antimicrobial Agents and Chemotherapy. 45, 1. 176-180 (2001)
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[Publications] Ohdo, S., Koyanagi, S., Suyama, H., Higuchi, S., Aramaki, H.: "Changing the dosing schedule minimizes the disruptive effects of interferon on clock function."Nature Medicine. 7, 3,. 356-360 (2001)
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[Publications] Takane, H., Ohdo, S., Baba, R., Koyanagi, S., Yukawa, E., Higuchi, S.: "Relationship between 24-hr rhythm in antiviral effect of interferon-β and interferon-α/β receptor expression in mice."Japanese Journal of Pharmacology. 90, 4. 304-312 (2002)
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[Publications] Akagi, T., Ushinohama, K., Kage, Y., Ishizaki, T., Makinosumi, T., Yamauchi, A., Taguchi, Y., Inoue K., Yukawa, E., Higuchi, S., Ohdo, S.: "Cell kinetics-dependent antitumor effect of irinotecan hydrochloride induced by the synchronizing effect of hydroxyurea: cell kinetics and dosing time."Life Sciences. 72. 1183-1197 (2003)
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「研究成果報告書概要(欧文)」より
