2002 Fiscal Year Final Research Report Summary
Molecular structure and function of uridine receptor regulating sleep
| Project/Area Number |
13672311
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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, 講師 (20234370)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAMOTO Ikuno Kyushu University of Health and Welfare, School of Pharmaceutical Sciences, Department of Hygienic Chemistry, Professor, 保健科学部, 教授 (50069746)
WATANABE Kazuhito Hokuriku University, Faculty of Pharmaceutical Sciences, Department of Hygienic Chemistry, Professor, 薬学部, 教授 (30113038)
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| Project Period (FY) |
2001 – 2002
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| Keywords | uridine / sleep / Uridine receptor / antinociception / nucleoside / Central nervous system / receptor |
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| Research Abstract |
The pyrimidine nucleosides including uridine are known to have central nervous system (CNS) depressant effects, such as hypnotic activity in mice. N^3-Benzyl and phenacyl derivatives of pyrimidine nucleosides were synthesized and their pharmacological effects on the CNS have been studied by intracerebroventricular injection to mice. We have found that N^3-benzyl or phenacyl substituted uridine and arabinofuranosyluracil exert antinociceptive activity in mice at a dose of 500 nmol/mouse. Systematic studies on structure-activity relationship of uridine related derivatives were performed to find stronger antinociceptive compounds, so that certain derivatives such as o- or p-fluorobenzyl-, o, m, p-chlo ; robenzyl-, o, m, p-bromobenzyl, p-chlorophenacyl substituted arabinofuranosyluracils exhibited 12-58 min of mice sleeping time. Moreover, o-fluorobenzyl- and o, p-bromobenzyl-arabinofuranosyluracils significantly potentiated pentobarbiral-induced sleep. Especially, p-chloro and p-bromo phenacyl derivatives exerted more potent antinociceptive activity than that of N^3-phenacyluridine. However, none of the N^3-benzyluridine derivatives except for N^3-(p-chlorobenzyl)uridine showed the antinociceptive activity. N^3-(2', 5' -dimethoxyphenacyl)uridine also exerted antinociceptive activities in mice. N^3-Phenacyluridine-6-carbonic acid was coupled with Affigel 102 and carbodiimide to prepare affinity column for using prurification of uridine receptor.
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