| Project/Area Number |
12557230
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
SATOH Masamchi Kyoto Univ., Grad. Sch. of Pharraaceu. Sci., Professor, 薬学研究科, 教授 (80025709)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAGAWA Takayuki Kyoto Univ., Grad. Sch. of Pharmaceu. Sci., Instructor, 薬学研究科, 助手 (30303845)
MINAMI Masabumi Kyoto Univ., Grad. Sch. of Pharmaceu. Sci., Assistant Professor, 薬学研究科, 助教授 (20243040)
SAJI Hideo Kyoto Univ.,Grad.Sch.of Pharmaceu.Sci., Professor, 薬学研究科, 教授 (40115853)
IWAMURA Tatsunori Gifu Pharmaceu. Univ., Dept. of Organic Chem., Assistant Professor, 薬学部, 講師 (70184900)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥13,400,000 (Direct Cost: ¥13,400,000)
Fiscal Year 2001: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2000: ¥10,100,000 (Direct Cost: ¥10,100,000)
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| Keywords | PET ligand / Opioid receptor / Carfentanil / Pain / Imaging / Binding activity / Endogenous ligand / Structure-activity relationships |
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| Research Abstract |
μ-Opioid receptors and their endogenous ligand are involved in the regulation of sensory and affective components of the pain experience. However, the molecular basis of the roles of opioidergic system in the higher brain functions, such as emotion and memory, remains to be elucidated. In this study, we studied on the synthesis and structure-activity relationships μ-opioid ligand to develop novel μ-selective nonpeptidic ligands which can be used for the positron emission tomography (PET) study. We synthesized several 1-aralky-4-phenylaminopiperidinecarboxylate derivatives and examined the binding affinity for μ-, δ-, κ- opioid and nociceptin receptors using the cell lines expressing the each of these receptors. 1-[2(2-Naphthyl)ethyl] -4- [(1-oxopropyl) phenylamino] -4-piperidinecarboxylic acid methyl ester exhibited the selective μ-opioid receptor binding activity. The Ki values of the compound were 5.6 nM for μ-, 3100 nM for δ-, and 5400 nM for K-receptor, respectively. The receptor-selectivity ratios were shown as δ/μ = 550 and κ/μ = 960. In addition, this compound showed no detectable affinity on a nociceptin receptor (Ki > 1 0000 nM). The experiment using the cell line expressing the cloned μ-opioid receptors revealed that this compound acted as a (μ-receptor agonist. This novel nonpeptidic ligand that is highly selective to μ-opioid receptors can be a useful tool for opioid pharmacology and PET study.
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