Pharmacological Characterization of Dezocine, a Potent Analgesic Acting as a kappa Partial Agonist and mu Partial Agonist

doi:10.1038/s41598-018-32568-y

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第二研究室

	Pharmacological Characterization of Dezocine, a Potent Analgesic Acting as a kappa Partial Agonist and mu Partial Agonist
	Wang, Yu-Hua 2; Chai, Jing-Rui 3,4; Xu, Xue-Jun 3,4; Ye, Ru-Feng 3,4; Zan, Gui-Ying 3,4; Liu, George Yun-Kun 5; Long, Jian-Dong 3,4; Ma, Yan 1; Huang, Xiang 3,4; Xiao, Zhi-Chao 3,4
刊名	SCIENTIFIC REPORTS
	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.
资助项目	National Natural Foundation of China[81773710] ; Youth Innovation Promotion Association of the Chinese Academy of Sciences[2017334]
WOS关键词	OPIOID RECEPTOR AGONIST ; INDUCED ANTINOCICEPTION ; ANTAGONIST PROPERTIES ; ANIMAL PHARMACOLOGY ; BUPRENORPHINE ; MORPHINE ; AGENT ; MICE ; ARIPIPRAZOLE ; PENTAZOCINE
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000445079400008
内容类型	期刊论文
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).