6aR-11-Amino-N-propyl-noraporphine, a new dopamine D2 and serotonin 5-HT1A dual agonist, elicits potent antiparkinsonian action and attenuates levodopa-induced dyskinesia in a 6-OHDA-lesioned rat model of Parkinson's disease

Rui Zhao, Weijian Lu, Xing Fang, Lin Guo, Zhi Yang, Na Ye, Jiahao Zhao, Zhili Liu, Jia Jia, Longtai Zheng, Bin Zhao, Ao Zhang, Xuechu Zhen

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Parkinson's disease (PD) drug therapy remains a challenge. Dual modulation of dopamine and 5-HT receptors has emerged as a promising approach in anti-PD drug development. Taking advantage of the newly discovered aporphine analogue(s), (6aR)-11-amino-N-propyl-noraporphine (SOMCL-171), which exhibited dual D2/5-HT1A receptor agonistic activity, we studied the effects of the compound on levodopa-induced dyskinesia (LID) in a PD animal model. The results demonstrated that SOMCL-171 elicited a potent anti-PD effect in a 6-OHDA-lesioned rat model. Chronic use of SOMCL-171 reduced LID without compromising the antiparkinsonian efficacy. Furthermore, we found that the antidyskinesia effect of SOMCL-171 is associated with its 5-HT1A agonistic activity and the up-regulation of the striatal 5-HT1A receptor. The present data indicated that chronic SOMCL-171 alone produced potent antiparkinsonian effects with weak dyskinesia, compared with that of levodopa. In addition, chronic SOMCL-171 application attenuated the development of levodopa-induced LID at no expense to the antiparkinsonian efficacy. Taken together, our data suggested that dual modulation of D2/5-HT 1A receptors may provide a novel approach for drug development in PD and LID.

Original languageEnglish (US)
Pages (from-to)204-210
Number of pages7
JournalPharmacology Biochemistry and Behavior
Volume124
DOIs
StatePublished - 2014
Externally publishedYes

Fingerprint

Serotonin 5-HT1 Receptor Agonists
Antiparkinson Agents
Oxidopamine
Dyskinesias
Levodopa
Parkinson Disease
Rats
Dopamine
Serotonin
Receptor, Serotonin, 5-HT1A
Modulation
Drug therapy
Corpus Striatum
Serotonin Receptors
Pharmaceutical Preparations
11-amino-N-propylnoraporphine
Animals
Up-Regulation
Animal Models
Drug Therapy

Keywords

  • L-DOPA-induced dyskinesia
  • Parkinson disease

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Pharmacology
  • Toxicology
  • Behavioral Neuroscience
  • Biological Psychiatry
  • Medicine(all)

Cite this

6aR-11-Amino-N-propyl-noraporphine, a new dopamine D2 and serotonin 5-HT1A dual agonist, elicits potent antiparkinsonian action and attenuates levodopa-induced dyskinesia in a 6-OHDA-lesioned rat model of Parkinson's disease. / Zhao, Rui; Lu, Weijian; Fang, Xing; Guo, Lin; Yang, Zhi; Ye, Na; Zhao, Jiahao; Liu, Zhili; Jia, Jia; Zheng, Longtai; Zhao, Bin; Zhang, Ao; Zhen, Xuechu.

In: Pharmacology Biochemistry and Behavior, Vol. 124, 2014, p. 204-210.

Research output: Contribution to journalArticle

Zhao, Rui ; Lu, Weijian ; Fang, Xing ; Guo, Lin ; Yang, Zhi ; Ye, Na ; Zhao, Jiahao ; Liu, Zhili ; Jia, Jia ; Zheng, Longtai ; Zhao, Bin ; Zhang, Ao ; Zhen, Xuechu. / 6aR-11-Amino-N-propyl-noraporphine, a new dopamine D2 and serotonin 5-HT1A dual agonist, elicits potent antiparkinsonian action and attenuates levodopa-induced dyskinesia in a 6-OHDA-lesioned rat model of Parkinson's disease. In: Pharmacology Biochemistry and Behavior. 2014 ; Vol. 124. pp. 204-210.
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abstract = "Parkinson's disease (PD) drug therapy remains a challenge. Dual modulation of dopamine and 5-HT receptors has emerged as a promising approach in anti-PD drug development. Taking advantage of the newly discovered aporphine analogue(s), (6aR)-11-amino-N-propyl-noraporphine (SOMCL-171), which exhibited dual D2/5-HT1A receptor agonistic activity, we studied the effects of the compound on levodopa-induced dyskinesia (LID) in a PD animal model. The results demonstrated that SOMCL-171 elicited a potent anti-PD effect in a 6-OHDA-lesioned rat model. Chronic use of SOMCL-171 reduced LID without compromising the antiparkinsonian efficacy. Furthermore, we found that the antidyskinesia effect of SOMCL-171 is associated with its 5-HT1A agonistic activity and the up-regulation of the striatal 5-HT1A receptor. The present data indicated that chronic SOMCL-171 alone produced potent antiparkinsonian effects with weak dyskinesia, compared with that of levodopa. In addition, chronic SOMCL-171 application attenuated the development of levodopa-induced LID at no expense to the antiparkinsonian efficacy. Taken together, our data suggested that dual modulation of D2/5-HT 1A receptors may provide a novel approach for drug development in PD and LID.",
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AU - Zhao, Rui

AU - Lu, Weijian

AU - Fang, Xing

AU - Guo, Lin

AU - Yang, Zhi

AU - Ye, Na

AU - Zhao, Jiahao

AU - Liu, Zhili

AU - Jia, Jia

AU - Zheng, Longtai

AU - Zhao, Bin

AU - Zhang, Ao

AU - Zhen, Xuechu

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