Pharmacological Characterization of Dezocine, a Potent Analgesic Acting as a kappa Partial Agonist and mu Partial Agonist
文献类型：期刊论文
| 作者 | Wang, Yu-Hua2; Chai, Jing-Rui3,4; Xu, Xue-Jun3,4; Ye, Ru-Feng3,4; Zan, Gui-Ying3,4; Liu, George Yun-Kun5; Long, Jian-Dong3,4; Ma, Yan1; Huang, Xiang3,4; Xiao, Zhi-Chao3,4 |
| 刊名 | SCIENTIFIC REPORTS
 |
| 出版日期 | 2018-09-20 |
| 卷号 | 8 |
| ISSN号 | 2045-2322 |
| DOI | 10.1038/s41598-018-32568-y |
| 文献子类 | Article |
| 英文摘要 | Dezocine is becoming dominated in China market for relieving moderate to severe pain. It is believed that Dezocine's clinical efficacy and little chance to provoke adverse events during the therapeutic process are mainly attributed to its partial agonist activity at the mu opioid receptor. In the present work, we comprehensively studied the pharmacological characterization of Dezocine and identified that the analgesic effect of Dezocine was a result of action at both the kappa and mu opioid receptors. We firstly found that Dezocine displayed preferential binding to mu opioid receptor over kappa and delta opioid receptors. Dezocine, on its own, weakly stimulated G protein activation in cells expressing kappa and mu receptors, but in the presence of full kappa agonist U50,488 H and mu agonist DAMGO, Dezocine inhibited U50,488H- and DAMGO-mediated G protein activation, indicating that Dezocine was a kappa partial agonist and p, partial agonist. Then the in intro results were verified by in vivo studies in mice. We observed that Dezocine-produced antinociception was significantly inhibited by kappa antagonist nor-BNI and mu antagonist beta-FNA pretreatment, indicating that Dezocine-mediated antinociception was via both the kappa and mu opioid receptors. When co-administrating of Dezocine with U50,488 H or morphine, Dezocine was capable of inhibiting U50,488H- or morphine-induced antinociception. Finally, kappa receptor activation-associated side effect sedation was investigated. We found that Dezocine displayed limited sedative effect with a ceiling effecting at a moderate dose. Thus, our work led to a better understanding of the analgesic mechanism of action of Dezocine in vivo. |
| WOS关键词 | OPIOID RECEPTOR AGONIST ; INDUCED ANTINOCICEPTION ; ANTAGONIST PROPERTIES ; ANIMAL PHARMACOLOGY ; BUPRENORPHINE ; MORPHINE ; AGENT ; MICE ; ARIPIPRAZOLE ; PENTAZOCINE |
| 资助项目 | National Natural Foundation of China[81773710] ; Youth Innovation Promotion Association of the Chinese Academy of Sciences[2017334] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:000445079400008 |
| 出版者 | NATURE PUBLISHING GROUP |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279574]  |
| 专题 | 药理学第二研究室 |
| 通讯作者 | Wang, Yu-Jun |
| 作者单位 | 1.Shanghai Univ, Sch Life Sci, Shanghai 200444, Peoples R China 2.Nanjing Univ Chinese Med, Sch Pharm, Nanjing 210046, Jiangsu, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, Key Lab Receptor Res, Shanghai 201203, Peoples R China; 4.Chinese Acad Sci, Collaborat Innovat Ctr Brain Sci, Shanghai 201203, Peoples R China; 5.Dublin Coffman High Sch, Dublin, OH 43017 USA; |
| 推荐引用方式 GB/T 7714 | Wang, Yu-Hua,Chai, Jing-Rui,Xu, Xue-Jun,et al. Pharmacological Characterization of Dezocine, a Potent Analgesic Acting as a kappa Partial Agonist and mu Partial Agonist[J]. SCIENTIFIC REPORTS,2018,8. |
| APA | Wang, Yu-Hua.,Chai, Jing-Rui.,Xu, Xue-Jun.,Ye, Ru-Feng.,Zan, Gui-Ying.,...&Wang, Yu-Jun.(2018).Pharmacological Characterization of Dezocine, a Potent Analgesic Acting as a kappa Partial Agonist and mu Partial Agonist.SCIENTIFIC REPORTS,8. |
| MLA | Wang, Yu-Hua,et al."Pharmacological Characterization of Dezocine, a Potent Analgesic Acting as a kappa Partial Agonist and mu Partial Agonist".SCIENTIFIC REPORTS 8(2018). |
入库方式： OAI收割
来源：上海药物研究所
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