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 profile

Hai Zhang, Na Ye, Shanglin Zhou, Lin Guo, Longtai Zheng, Zhili Liu, Bo Gao, Xuechu Zhen, Ao Zhang

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34 Scopus citations

Abstract

A series of new aporphine analogues (aporlogues) were synthesized bearing a C-, N-, or O-linkage at the C11 position. Lipoic ester (-)-15 was identified as a full agonist at the dopamine D2 and serotonin 5-HT1A receptors with Ki values of 174 and 66 nM, respectively. It elicited antiparkinsonian action on Parkinsin's disease (PD) rats with minor dyskinesia. Chronic use of (-)-15 reduced l-DOPA-induced dyskinesia (LID) without attenuating the antiparkinsonian effect. These results suggest that 5-HT 1A and D2 dual-receptor agonist (-)-15 may present a novel candidate drug in the treatment of PD and LID.

Original languageEnglish (US)
Pages (from-to)4324-4338
Number of pages15
JournalJournal of Medicinal Chemistry
Volume54
Issue number13
DOIs
StatePublished - Jul 14 2011

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ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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