Identification of a tool compound to study the mechanisms of functional selectivity between D-2 and D-3 dopamine receptors

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• dc.contributor.author Reyes-Resina, Irene
• dc.contributor.author Samadi, Abdelouahid
• dc.contributor.author Navarro, Gemma
• dc.contributor.author Saadeh, Haythem A.
• dc.contributor.author Khasawneh, Mohammad A.
• dc.contributor.author Mestres i López, Jordi
• dc.contributor.author Marco-Contelles, José
• dc.contributor.author Franco, Rafael
• dc.date.accessioned 2020-05-06T07:07:46Z
• dc.date.available 2020-05-06T07:07:46Z
• dc.date.issued 2018
• dc.description.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.
• dc.format.mimetype application/pdf
• dc.identifier.citation Reyes-Resina I, Samadi A, Navarro G, Saadeh H. A., Khasawneh M. A. , Mestres i López J, Marco-Contelles, J. Identification of a tool compound to study the mechanisms of functional selectivity between D-2 and D-3 dopamine receptors. ACS Omega 2018; 3(12): 17368-75. DOI: 10.1021/acsomega.8b02509
• dc.identifier.doi http://dx.doi.org/10.1021/acsomega.8b02509
• dc.identifier.issn 2470-1343
• dc.identifier.uri http://hdl.handle.net/10230/44420
• dc.language.iso eng
• dc.publisher American Chemical Society (ACS)
• dc.relation.ispartof ACS Omega. 2018;3(12):17368-75
• dc.rights This is an open access article published under an ACS Author Choice License, which permits copying and redistribution of the article or any adaptations for non-commercial purpose
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.subject.keyword N-Arylpiperazines
• dc.subject.keyword 5-((4-Arylpiperazin-1-yl)methyl)quinolin-8-ols
• dc.subject.keyword Biased agonism
• dc.subject.keyword Dopaminergic transmission
• dc.subject.keyword Functional selectivity
• dc.subject.keyword G-protein-coupled receptors
• dc.subject.keyword 5-((4-(Pyrimidin-2-yl)piperazin-1-yl)methyl)quinolin-8-ol
• dc.subject.keyword 5-((4-(Pyrimidin-2-yl)piperazin-1-yl)methyl)quinolin-8-ol
• dc.subject.keyword Synthesis
• dc.title Identification of a tool compound to study the mechanisms of functional selectivity between D-2 and D-3 dopamine receptors
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion