Dual Ligands Targeting Dopamine D-2 and Serotonin 5-HT1A Receptors as New Antipsychotical or Anti-Parkinsonian Agents

	Dual Ligands Targeting Dopamine D-2 and Serotonin 5-HT1A Receptors as New Antipsychotical or Anti-Parkinsonian Agents
	Ye, Na ; Song, Zilan ; Zhang, Ao1,2
刊名	CURRENT MEDICINAL CHEMISTRY
	2014-02
卷号	21 期号:4 页码:437-457
关键词	Atypical antipsychotics dopamine D-2 receptor dual ligands Parkinson's disease Schizophrenia Serotonin 5-HT1A receptor
ISSN号	0929-8673
文献子类	Article
英文摘要	Psychiatric disorders like schizophrenia and neurode generative diseases like Parkinson's disease are associated with poly-factorial pathogenic mechanisms, with several neurotransmitter systems closely involved. In addition to the cerebral dopaminergic (DA) system, the serotoninergic (5-HT) system also plays a crucial role in regulating psycho-emotional, cognitive and motor functions in the central nervous system (CNS). Among the large 5-HT receptor family, accumulating data have revealed new insights into the therapeutic benefit of the 5-HT1A receptor in treating various CNS disorders, especially schizophrenia and Parkinson's disease. The present review discusses the advance of dual agents with mixed actions at the dopamine D-2 and serotonin 5-HT1A receptors in the treatment of these diseases. Aripiprazole was the only marketed drug with dual D-2 and 5-HT1A profile. It is a partial D-2 and 5-HT1A receptor agonist and has been prescribed as an atypical antipsychotical drug. Two other drugs Cariprazine and Pardoprunox are being investigated in clinic. Most of the other candidate compounds, including Bifeprunox, Sarizotan, Mazapertine succinate, PF-217830, and Adoprazine were discontinued due to either non-optimal pharmacokinetic properties or insufficient therapeutical efficacy. Although much effort has been done to highlight the advantages of the 5-HT1A and D-2 dual approach, it has to be pointed out that many of these drugs showed poly-pharmacological profile by targeting many other receptors and/or transporters besides the D-2 and 5-HT1A receptors. In this regard, 'pure' compounds exclusively acting on the D-2 and 5-HT1A receptors are highly needed to further validate this approach. Meanwhile, safety concerns and in vivo pharmacokinetic alerts should also be implanted to the drug design art early.
资助项目	Chinese NSF[81125021] ; Chinese NSF[81373277] ; National Science & Technology Major Project on 'Key New Drug Creation and Manufacturing Program', China[2012ZX09103-101-035] ; National Science & Technology Major Project on 'Key New Drug Creation and Manufacturing Program', China[2012ZX 09301001-001] ; Interdisciplinary Cooperation Team" Program for Science and Technology Innovation (CAS)[00000000] ; National Program on Key Basic Research Project of China[2012CB910704] ; State Key Laboratory of Drug Research[SIMM1302KF-08] ; Shanghai Institute of Materia Medica[00000000]
WOS关键词	HALOPERIDOL-INDUCED CATALEPSY ; POTENTIAL ATYPICAL ANTIPSYCHOTICS ; RESTRICTED BENZAMIDE ANALOGS ; CENTRAL-NERVOUS-SYSTEM ; L-DOPA THERAPY ; AGONIST PROPERTIES ; IN-VIVO ; APORPHINE ENANTIOMERS ; NEUROCHEMICAL PROFILE ; BINDING-PROPERTIES
WOS研究方向	Biochemistry & Molecular Biology ; Pharmacology & Pharmacy
语种	英语
出版者	BENTHAM SCIENCE PUBL LTD
WOS记录号	WOS:000331447700003
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277203]
专题	药物化学研究室
通讯作者	Zhang, Ao
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Synthet Organ & Med Chem Lab, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Ye, Na,Song, Zilan,Zhang, Ao. Dual Ligands Targeting Dopamine D-2 and Serotonin 5-HT1A Receptors as New Antipsychotical or Anti-Parkinsonian Agents[J]. CURRENT MEDICINAL CHEMISTRY,2014,21(4):437-457.
APA	Ye, Na,Song, Zilan,&Zhang, Ao.(2014).Dual Ligands Targeting Dopamine D-2 and Serotonin 5-HT1A Receptors as New Antipsychotical or Anti-Parkinsonian Agents.CURRENT MEDICINAL CHEMISTRY,21(4),437-457.
MLA	Ye, Na,et al."Dual Ligands Targeting Dopamine D-2 and Serotonin 5-HT1A Receptors as New Antipsychotical or Anti-Parkinsonian Agents".CURRENT MEDICINAL CHEMISTRY 21.4(2014):437-457.