Dopamine D3 receptor ligand suppresses the expression of levodopa-induced dyskinesia in nonhuman primate model of parkinson's disease

Thomas Oh, Elyas S. Daadi, Jeffrey Kim, Etienne W. Daadi, Peng Jen Chen, Gourav Roy-Choudhury, Jonathan Bohmann, Benjamin E. Blass, Marcel M. Daadi

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Parkinson's disease (PD) is a complex multisystem, chronic and so far incurable disease with significant unmet medical needs. The incidence of PD increases with aging and the expected burden will continue to escalate with our aging population. Since its discovery in the 1961 levodopa has remained the gold standard pharmacotherapy for PD. However, the progressive nature of the neurodegenerative process in and beyond the nigrostriatal system causes a multitude of side effects, including levodopa-induced dyskinesia within 5 years of therapy. Attenuating dyskinesia has been a significant challenge in the clinical management of PD. We report on a small molecule that eliminates the expression of levodopa-induced dyskinesia and significantly improves PD-like symptoms. The lead compound PD13R we discovered is a dopamine D3 receptor partial agonist with high affinity and selectivity, orally active and with desirable drug-like properties. Future studies are aimed at developing this lead compound for treating PD patients with dyskinesia.

Original languageEnglish (US)
Article number113920
JournalExperimental Neurology
Volume347
DOIs
StatePublished - Jan 2022

Keywords

  • Actigraphy
  • Arylpiperazine pharmacophore
  • D3 receptor
  • Levodopa-induced dyskinesia
  • Nonhuman primate model of dyskinesia
  • Parkinson's disease
  • Sleep disturbances

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

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