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

doi:10.1021/jm200347t

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-HT_1A 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 journal › Article › peer-review

35 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-HT_1A receptors with K_i 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 language	English (US)
Pages (from-to)	4324-4338
Number of pages	15
Journal	Journal of medicinal chemistry
Volume	54
Issue number	13
DOIs	https://doi.org/10.1021/jm200347t
State	Published - Jul 14 2011
Externally published	Yes

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

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title = "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",

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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T1 - 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

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

PY - 2011/7/14

Y1 - 2011/7/14

N2 - 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.

AB - 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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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-HT_1A dual-agonist profile

Abstract

ASJC Scopus subject areas

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