(6aR)-11-Amino-N-propyl-noraporphine, a new dopamine D-2 and serotonin 5-HT1A dual agonist, elicits potent antiparkinsonian action and attenuates levodopa-induced dyskinesia in a 6-OHDA-lesioned rat model of Parkinson's disease

doi:10.1016/j.pbb.2014.06.011

	(6aR)-11-Amino-N-propyl-noraporphine, a new dopamine D-2 and serotonin 5-HT1A dual agonist, elicits potent antiparkinsonian action and attenuates levodopa-induced dyskinesia in a 6-OHDA-lesioned rat model of Parkinson's disease
	Zhao, Rui 1,2; Lu, Weijian 1,2; Fang, Xing 1,2; Guo, Lin 1,2; Yang, Zhi 4; Ye, Na 3; Zhao, Jiahao 4; Liu, Zhili 3; Jia, Jia 1,2; Zheng, Longtai 1,2
刊名	PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
	2014-09
卷号	124 页码:204-210
关键词	Dopamine-D-2 receptor L-DOPA-induced dyskinesia Parkinson disease 5-HT1A receptor
ISSN号	0091-3057
DOI	10.1016/j.pbb.2014.06.011
文献子类	Article
英文摘要	Parkinson's disease (PD) drug therapy remains a challenge. Dual modulation of dopamine and 5-HT receptors has emerged as a promising approach in anti-PD drug development. Taking advantage of the newly discovered aporphine analogue(s), (6aR)-11-amino-N-propyl-noraporphine (SOMCL-171), which exhibited dual D-2/5-HT1A receptor agonistic activity, we studied the effects of the compound on levodopa-induced dyskinesia (LID) in a PD animal model. The results demonstrated that SOMCL-171 elicited a potent anti-PD effect in a 6-OHDA-lesioned rat model, Chronic use of SOMCL-171 reduced LID without compromising the antiparkinsonian efficacy. Furthermore, we found that the antidyskinesia effect of SOMCL-171 is associated with its 5-HT1A agonistic activity and the up-regulation of the striatal 5-HT1A receptor. The present data indicated that chronic SOMCL-171 alone produced potent antiparkinsonian effects with weak dyskinesia, compared with that of levodopa. In addition, chronic SOMCL-171 application attenuated the development of levodopa-induced LID at no expense to the antiparkinsonian efficacy. Taken together, our data suggested that dual modulation of D-2/5-HT1A receptors may provide a novel approach for drug development in PD and LID. (C) 2014 Elsevier Inc. All rights reserved.
资助项目	National Science Foundation of China[81130023] ; National Science Foundation of China[81125021] ; National Science Foundation of China[811373382] ; National Science Foundation of China[81100918] ; National Basic Research Plan (973) of the Ministry of Science and Technology of China[2009CB522000] ; National Basic Research Plan (973) of the Ministry of Science and Technology of China[2011CB5C4403] ; Priority Academic Program Development of Jiangsu Higher Education Institutes[00000000]
WOS关键词	DOPA-INDUCED DYSKINESIA ; 5-HYDROXYTRYPTAMINE 5-HT ; RECEPTOR AGONIST ; IDENTIFICATION ; MECHANISMS
WOS研究方向	Behavioral Sciences ; Neurosciences & Neurology ; Pharmacology & Pharmacy
语种	英语
出版者	PERGAMON-ELSEVIER SCIENCE LTD
WOS记录号	WOS:000343621900029
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276914]
专题	药物化学研究室药理学第二研究室
通讯作者	Zhang, Ao
作者单位	1.Soochow Univ, Coll Pharmaceut Sci, Jiangsu Key Lab Translat Res & Therapy Neuropsych, Suzhou, Peoples R China; 2.Soochow Univ, Coll Pharmaceut Sci, Dept Pharmacol, Suzhou 215000, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, Synthet Organ & Med Chem Lab, Shanghai 201203, Peoples R China; 4.Guangdong Med Coll, Affiliated Hosp, Dept Neurol, Zhanjiang, Guangdong, Peoples R China
推荐引用方式 GB/T 7714	Zhao, Rui,Lu, Weijian,Fang, Xing,et al. (6aR)-11-Amino-N-propyl-noraporphine, a new dopamine D-2 and serotonin 5-HT1A dual agonist, elicits potent antiparkinsonian action and attenuates levodopa-induced dyskinesia in a 6-OHDA-lesioned rat model of Parkinson's disease[J]. PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR,2014,124:204-210.
APA	Zhao, Rui.,Lu, Weijian.,Fang, Xing.,Guo, Lin.,Yang, Zhi.,...&Zhen, Xuechu.(2014).(6aR)-11-Amino-N-propyl-noraporphine, a new dopamine D-2 and serotonin 5-HT1A dual agonist, elicits potent antiparkinsonian action and attenuates levodopa-induced dyskinesia in a 6-OHDA-lesioned rat model of Parkinson's disease.PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR,124,204-210.
MLA	Zhao, Rui,et al."(6aR)-11-Amino-N-propyl-noraporphine, a new dopamine D-2 and serotonin 5-HT1A dual agonist, elicits potent antiparkinsonian action and attenuates levodopa-induced dyskinesia in a 6-OHDA-lesioned rat model of Parkinson's disease".PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR 124(2014):204-210.