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論文
- タイトル
- タイトル（英）
- Effects of the novel selective κ-opioid receptor agonist NP-5497-KA on morphine-induced reward-related behaviors
- 参照URL
- https://researchmap.jp/read0201960/published_papers/43878464
- 著者
- 著者（英）
- Soichiro Ide,Toshitake Hirai,Takafumi Muto,Tomio Yamakawa,Kazutaka Ikeda
- 担当区分
- 概要
- 概要（英）
- Abstract Opioid addiction and the opioid overdose epidemic are becoming more serious, and the development of therapeutic agents is essential for the pharmacological treatment of substance use disorders. The κ-opioid receptor (KOP) is a member of the opioid receptor system that has been gaining attention as a promising molecular target for the treatment of numerous human disorders, including pain, depression, anxiety, and drug addiction. Here, we biologically and pharmacologically evaluated a novel azepane-derived ligand, NP-5497-KA, as a selective KOP agonist. NP-5497-KA had 1000-fold higher selectivity for the KOP over the μ-opioid receptor (MOP), which was higher than nalfurafine (KOP/MOP: 65-fold), and acted as a selective KOP full agonist in the 3′,5′-cyclic adenosine monophosphate assay. The oral administration of NP-5497-KA (1–10 mg/kg) dose-dependently suppressed morphine-induced conditioned place preference in C57BL/6 J mice, and its effects were comparable to an intraperitoneal injection of nalfurafine (1–10 μg/kg). Nalfurafine (10 μg/kg) significantly inhibited rotarod performance, whereas NP-5497-KA (10 mg/kg) exerted no effect on rotarod performance. These results indicate that NP-5497-KA may be a novel option for the treatment of opioid use disorder with fewer side effects.
- 出版者・発行元
- 出版者・発行元（英）
- Springer Science and Business Media LLC
- 誌名
- 誌名（英）
- Scientific Reports
- 巻
- 13
- 号
- 1
- 開始ページ
- 終了ページ
- 出版年月
- 2023年10月24日
- 査読の有無
- 招待の有無
- 掲載種別
- 研究論文（学術雑誌）
- ISSN
- DOI URL
- https://doi.org/10.1038/s41598-023-45584-4
- 共同研究・競争的資金等の研究課題