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

Research output: Contribution to journalArticle

29 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Serotonin 5-HT1 Receptor Agonists
Dyskinesias
Antiparkinson Agents
Dopamine
Serotonin
Receptor, Serotonin, 5-HT1A
Dopamine Agonists
Esters
Pharmaceutical Preparations
N-propylnoraporphin-11-yl 5-(1,2-dithiolan-3-yl)pentanoate

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

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

In: Journal of Medicinal Chemistry, Vol. 54, No. 13, 14.07.2011, p. 4324-4338.

Research output: Contribution to journalArticle

Zhang, Hai ; Ye, Na ; Zhou, Shanglin ; Guo, Lin ; Zheng, Longtai ; Liu, Zhili ; Gao, Bo ; Zhen, Xuechu ; Zhang, Ao. / 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. In: Journal of Medicinal Chemistry. 2011 ; Vol. 54, No. 13. pp. 4324-4338.
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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.",
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AU - Zhang, Hai

AU - Ye, Na

AU - Zhou, Shanglin

AU - Guo, Lin

AU - Zheng, Longtai

AU - Liu, Zhili

AU - Gao, Bo

AU - Zhen, Xuechu

AU - Zhang, Ao

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