Dopamine D₄ Receptor-Selective Compounds Reveal Structure-Activity Relationships that Engender Agonist Efficacy.

ABSTRACT: The dopamine D₄ receptor (D₄R) plays important roles in cognition, attention, and decision making. Novel D₄R-selective ligands have promise in medication development for neuropsychiatric conditions, including Alzheimer's disease and substance use disorders. To identify new D₄R-selective ligands, and to understand the molecular determinants of agonist efficacy at D₄R, we report a series of eighteen novel ligands based on the classical D₄R agonist A-412997 (1, 2-(4-(pyridin-2-yl)piperidin-1-yl)- N-( m-tolyl)acetamide). Compounds were profiled using radioligand binding displacement assays, β-arrestin recruitment assays, cyclic AMP inhibition assays, and molecular dynamics computational modeling. We identified several novel D

SUBMITTER: Keck TM 

PROVIDER: S-EPMC6466480 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature