Identification of a Tool Compound to Study the Mechanisms of Functional Selectivity between D2 and D3 Dopamine Receptors

Irene Reyes-Resina, Abdelouahid Samadi, Gemma Navarro, Haythem A. Saadeh, Mohammad A. Khasawneh, Jordi Mestres, José Marco-Contelles, Rafael Franco

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

The search for synthetic selective compounds for G-protein-coupled receptors has provided a myriad of molecules with high selectivity and therapeutic potential. In some cases, however, selectivity is difficult to obtain. For instance, the selectivity ratio is relatively low for compounds acting on D2 and D3 dopamine receptors, which are targets of neurodegenerative diseases such as Parkinson's and Huntington's. From a therapeutic point of view, it is of interest the relative recent discovery of biased agonism, which is characterized by different signaling pathways engaged by different compounds acting on a given receptor. The aim of this paper was to investigate whether new piribedil-derived compounds could display higher selectivity for D2 or D3 receptor and/or provide biased signaling. The results show that selectivity was not different, but that one of the molecules described here, 5-((4-(pyrimidin-2-yl)piperazin-1-yl)methyl)quinolin-8-ol (10), does engage Gi-mediated signaling via D2 or D3 receptors, whereas it does not activate the mitogen-activated-protein kinase pathway, which is usually activated by dopamine receptor agonists.

Original languageEnglish
Pages (from-to)17368-17375
Number of pages8
JournalACS Omega
Volume3
Issue number12
DOIs
Publication statusPublished - Dec 14 2018

ASJC Scopus subject areas

  • General Chemistry
  • General Chemical Engineering

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