Identification of G protein-biased agonists that fail to recruit β-arrestin or promote internalization of the D1 dopamine receptor.

ABSTRACT: The D1 dopamine receptor (D1R) has been implicated in numerous neuropsychiatric disorders, and D1R-selective ligands have potential as therapeutic agents. Previous studies have identified substituted benzazepines as D1R-selective agonists, but the in vivo effects of these compounds have not correlated well with their in vitro pharmacological activities. A series of substituted benzazepines, and structurally dissimilar D1R-selective agonists, were tested for their functional effects on D1R-mediated cAMP accumulation, D1R-promoted β-arrestin recruitment, and D1R internalization using live cell functional assays. All compounds tested elicited an increase in the level of cAMP accumulation, albeit with a range of efficacies. However, when the compounds were evaluated for β-arrestin recruitment,

SUBMITTER: Conroy JL 

PROVIDER: S-EPMC5234767 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature