Hypnotic and antinociceptive effects of N3-substituted oxopyrimidines and their mechanism
| Project/Area Number |
15590075
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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 |
Biological pharmacy
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| Research Institution | Hokuriku University |
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Principal Investigator |
KIMURA Toshiyuki Hokuriku University, Faculty of Pharmaceutical Sciences, Department of Hygienic Chemistry, Associate Professor, 薬学部, 助教授 (20234370)
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| Co-Investigator(Kenkyū-buntansha) |
WATANABE Kazuhito Hokuriku University, Faculty of Pharmaceutical Sciences, Department of Hygienic Chemistry, Professor, 薬学部, 教授 (30113038)
FUNAHASHI Tatsuya Hokuriku University, Faculty of Pharmaceutical Sciences, Department of Hygienic Chemistry, Research Assistant, 薬学部, 助手 (60343646)
YAMAORI Satoshi Hokuriku University, Faculty of Pharmaceutical Sciences, Department of Hygienic Chemistry, Research Assistant, 薬学部, 助手 (40360218)
YAMAMOTO Ikuo Kyushu University of Health and Welfare, School of Pharmaceutical Sciences, Department of Hygienic Chemistry, Professor, 薬学部, 教授 (50069746)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2004: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2003: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | uridine / sleep / antinociceptive effect / nucleoside / uridine receptor / central nervous system |
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| Research Abstract |
N^3-Substituted oxopyrimidine nucleosides are known to possess central nervous system depressant effects such as hypnotic activity and antinociceptive effect. We synthesized N^3-substituted oxopyrimidine nucleosides such as benzyl, phenacyl and their related group substituted analogues. N^3-Nitrobenzyl and N^3-(2'-cyanobenzyl)-arabinofuranosyluracil possessed strong hypnotic activity at 2.0 umol/mouse by i.c.v. injection. N^3-(2',5'-Dimethoxyphenacyl)-arabinofuranosyluracil (N^3-(2',5'-DiMeOPhAc)-AraU) was found to exhibit the antinociceptive effects without the hypnotic activity in mice, and the effects was inhibited by naloxone. We report interaction of N^3-(2',5'-DiMeOPhAc)-AraU with opioid receptors using rat brain slice. SD male rat brain slice (20μm) was incubated with opioid ligand with/without N^3-(2',5'-DiMeOPhAc)-AraU. The radioactivity was measured by LSC and FUJI-FL2000. Bindings of [^3H]DAMGO (μ) and [^3H]DPDPE (δ) displaced by 100uM of N^3-(2',5'-DiMeOPhAc)-AraU, while binding of [^3H]U-69593 did not. Apparent decrease of the binding of μ, and δ receptors was recognized in cortex. In addition m receptor in striatum, hippocampus and thalamus was also decreased. These results indicated that antinociceptive effect of N^3(2',5'-DiMeOPhAc)-AraU was partly contributed μ, and δ opioid receptors.
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Report
(3 results)
Research Products
(2 results)
