Novel kappa-opioid receptor agonist MB-1C-OH produces potent analgesia with less depression and sedation

doi:10.1038/aps.2014.145

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

	Novel kappa-opioid receptor agonist MB-1C-OH produces potent analgesia with less depression and sedation
	Zhang, Le-sha 2,3; Wang, Jun 2,3,4; Chen, Jian-chun 1; Tao, Yi-min 2,3; Wang, Yu-hua 4,5; Xu, Xue-jun 2,3; Chen, Jie 2,3; Xu, Yun-gen 4; Xi, Tao 4; Hu, Xiao-wu 1
刊名	ACTA PHARMACOLOGICA SINICA
	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.
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关键词	FORMALIN TEST ; BEHAVIOR ; RATS ; MU ; ACTIVATION ; MORPHINE ; BINDING ; PAIN ; MICE ; DEPENDENCE
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
语种	英语
CSCD记录号	CSCD:5425430
出版者	ACTA PHARMACOLOGICA SINICA
WOS记录号	WOS:000353893100004
内容类型	期刊论文
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.