Identification of N-Propylnoraporphin-11-yl 5-(1,2-Dithiolan-3-yl)pentanoate as a New Anti-Parkinson's Agent Possessing a Dopamine D2 and Serotonin 5-HT1A Dual-Agonist Pro

详细信息    查看全文

• 作者：Hai Zhang ; Na Ye ; Shanglin Zhou ; Lin Guo ; Longtai Zheng ; Zhili Liu ; Bo Gao ; Xuechu Zhen ; Ao Zhang
• 刊名：Journal of Medicinal Chemistry
• 出版年：2011
• 出版时间：July 14, 2011
• 年：2011
• 卷：54
• 期：13
• 页码：4324-4338
• 全文大小：1229K
• 年卷期：v.54,no.13(July 14, 2011)
• ISSN：1520-4804

文摘

A series of new aporphine analogues (aporlogues) were synthesized bearing a C-, N-, or O-linkage at the C11 position. Lipoic ester (鈭?-15 was identified as a full agonist at the dopamine D₂ and serotonin 5-HT_1A receptors with K_i values of 174 and 66 nM, respectively. It elicited antiparkinsonian action on Parkinsin鈥檚 disease (PD) rats with minor dyskinesia. Chronic use of (鈭?-15 reduced l-DOPA-induced dyskinesia (LID) without attenuating the antiparkinsonian effect. These results suggest that 5-HT_1A and D₂ dual-receptor agonist (鈭?-15 may present a novel candidate drug in the treatment of PD and LID.