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• W2014862375 abstract "Many in vitro data show that some ligands can cause the differential activation of signaling pathways mediated by a single receptor (termed ‘functional selectivity’). It remains unclear, however, whether functionally selective properties are meaningful in vivo. Data obtained with experimental compounds that are functionally selective at the dopamine D2L receptor in vitro suggest that these properties might predict atypical behavioral actions. Moreover, the antipsychotic drug aripiprazole is commonly thought to be a D2 partial agonist, but data clearly show that aripiprazole is functionally selective in vitro. It is proposed that the effects of aripiprazole in animal models and humans can be reconciled only with its functionally selective D2 properties, not its partial D2 agonism. Together, these data provide support for the hypothesis that compounds with functionally selective properties in vitro are likely to have novel actions in vivo, opening doors to new avenues of drug discovery. Many in vitro data show that some ligands can cause the differential activation of signaling pathways mediated by a single receptor (termed ‘functional selectivity’). It remains unclear, however, whether functionally selective properties are meaningful in vivo. Data obtained with experimental compounds that are functionally selective at the dopamine D2L receptor in vitro suggest that these properties might predict atypical behavioral actions. Moreover, the antipsychotic drug aripiprazole is commonly thought to be a D2 partial agonist, but data clearly show that aripiprazole is functionally selective in vitro. It is proposed that the effects of aripiprazole in animal models and humans can be reconciled only with its functionally selective D2 properties, not its partial D2 agonism. Together, these data provide support for the hypothesis that compounds with functionally selective properties in vitro are likely to have novel actions in vivo, opening doors to new avenues of drug discovery." @default.
• W2014862375 created "2016-06-24" @default.
• W2014862375 creator A5075795856 @default.
• W2014862375 date "2007-08-01" @default.
• W2014862375 modified "2023-09-25" @default.
• W2014862375 title "GPCR functional selectivity has therapeutic impact" @default.
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• W2014862375 doi "https://doi.org/10.1016/j.tips.2007.06.002" @default.
• W2014862375 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2958218" @default.
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