Development of selective agonists for the morphine-insensitive opioid mu receptor splice variants
| Project/Area Number |
26460152
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Drug development chemistry
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| Research Institution | Kitasato University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
HIRAYAMA Shigeto 北里大学, 薬学部, 助教 (40565842)
SAKURADA Shinobu 東北医科薬科大学, 薬学部, 客員教授 (30075816)
MIZOGUCHI Hirokazu 東北医科薬科大学, 薬学部, 教授 (30360069)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | スプライスバリアント / オピオイド / μ受容体 / メサドン / モルヒナン |
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| Outline of Final Research Achievements |
To develop nonpeptidic agonists selective for the morphine-insensitive opioid mu receptor splice variants with which peptidic agonist amidino-TAPA can interact, we attempted to identify the pharmacophore for the splice variants. As a designed compound based on the methadone structure did not show any agonistic activities (antinociceptive effects), a working hypothesis that the Phe residue in amidino-TAPA would play an important role in eliciting its activities was not confirmed. The compounds evaluated in in vivo assays must have low or no binding affinities for the kappa receptor. Although we designed and synthesized several morphinan derivatives, only one compound among the synthesized ones fulfilled the criterion. Therefore, we have not yet found selective agonists. To achieve our investigation aims, we think that it is important to newly construct an in vitro assay which can evaluate the binding affinities and/or activities of the tested compounds for the splice variants.
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Report
(4 results)
Research Products
(8 results)
