Novel kappa-opioid receptor agonist MB-1C-OH produces potent analgesia with less depression and sedation
文献类型：期刊论文
| 作者 | Zhang, Le-sha2,3; Wang, Jun2,3,4; Chen, Jian-chun1; Tao, Yi-min2,3; Wang, Yu-hua4,5; Xu, Xue-jun2,3; Chen, Jie2,3; Xu, Yun-gen4; Xi, Tao4; Hu, Xiao-wu1 |
| 刊名 | ACTA PHARMACOLOGICA SINICA
 |
| 出版日期 | 2015-05 |
| 卷号 | 36期号:5页码:565-571 |
| 关键词 | kappa-opioid receptor MB-1C-OH (-)U50,488H Nor-BNI morphine pain acetic acid-induced writhing formalin test depression sedation |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/aps.2014.145 |
| 文献子类 | Article |
| 英文摘要 | Aim: To characterize the pharmacological profiles of a novel kappa-opioid receptor agonist MB-1C-OH. Methods: [H-3]diprenorphine binding and [S-35]GTP.S binding assays were performed to determine the agonistic properties of MB-1C-OH. Hot plate, tail flick, acetic acid-induced writhing, and formalin tests were conducted in mice to evaluate the antinociceptive actions. Forced swimming and rotarod tests of mice were used to assess the sedation and depression actions. Results: In [H-3]diprenorphine binding assay, MB-1C-OH did not bind to mu- and delta-opioid receptors at the concentration of 100 mu mol/L, but showed a high affinity for kappa-opioid receptor (kappa(i)=35 nmol/L). In [S-35]GTP gamma S binding assay, the compound had an E-max of 98% and an EC50 of 16.7 nmol/L for kappa-opioid receptor. Subcutaneous injection of MB-1C-OH had no effects in both hot plate and tail flick tests, but produced potent antinociception in the acetic acid-induced writhing test (ED50= 0.39 mg/kg), which was antagonized by pretreatment with a selective.-opioid receptor antagonist Nor-BNI. In the formalin test, subcutaneous injection of MB-1C-OH did not affect the flinching behavior in the first phase, but significantly inhibited that in the second phase (ED50=0.87 mg/kg). In addition, the sedation or depression actions of MB-1C-OH were about 3-fold weaker than those of the classical kappa agonist (-)U50,488H. Conclusion: MB-1C-OH is a novel kappa-opioid receptor agonist that produces potent antinociception causing less sedation and depression. |
| WOS关键词 | FORMALIN TEST ; BEHAVIOR ; RATS ; MU ; ACTIVATION ; MORPHINE ; BINDING ; PAIN ; MICE ; DEPENDENCE |
| 资助项目 | National Basic Research Program: a grant from the Ministry of Science and Technology of China[2009CB522005] ; National Natural Science Foundation of China[81130087] ; National Natural Science Foundation of China[81171296] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| CSCD记录号 | CSCD:5425430 |
| WOS记录号 | WOS:000353893100004 |
| 出版者 | ACTA PHARMACOLOGICA SINICA |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276553]  |
| 专题 | 药理学第二研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Wang, Yu-jun |
| 作者单位 | 1.Second Mil Med Univ, Changhai Hosp, Dept Neurosurg, Shanghai 200433, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 3.Chinese Acad Sci, Collaborat Innovat Ctr Brain Sci, Shanghai 201203, Peoples R China; 4.China Pharmaceut Univ, Sch Life Sci & Technol, Biotechnol Ctr, Nanjing 210009, Peoples R China; 5.Nanjing Univ Chinese Med, Sch Pharm, Nanjing 210046, Jiangsu, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhang, Le-sha,Wang, Jun,Chen, Jian-chun,et al. Novel kappa-opioid receptor agonist MB-1C-OH produces potent analgesia with less depression and sedation[J]. ACTA PHARMACOLOGICA SINICA,2015,36(5):565-571. |
| APA | Zhang, Le-sha.,Wang, Jun.,Chen, Jian-chun.,Tao, Yi-min.,Wang, Yu-hua.,...&Liu, Jing-gen.(2015).Novel kappa-opioid receptor agonist MB-1C-OH produces potent analgesia with less depression and sedation.ACTA PHARMACOLOGICA SINICA,36(5),565-571. |
| MLA | Zhang, Le-sha,et al."Novel kappa-opioid receptor agonist MB-1C-OH produces potent analgesia with less depression and sedation".ACTA PHARMACOLOGICA SINICA 36.5(2015):565-571. |
入库方式： OAI收割
来源：上海药物研究所
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