Functional Selectivity and Classical Concepts of Quantitative Pharmacology

@article{Urban2007FunctionalSA,
  title={Functional Selectivity and Classical Concepts of Quantitative Pharmacology},
  author={Jonathan D Urban and W. P. Clarke and M. von Zastrow and D. Nichols and B. Kobilka and H. Weinstein and J. Javitch and B. Roth and A. Christopoulos and P. Sexton and K. Miller and M. Spedding and R. Mailman},
  journal={Journal of Pharmacology and Experimental Therapeutics},
  year={2007},
  volume={320},
  pages={1 - 13}
}
  • Jonathan D Urban, W. P. Clarke, +10 authors R. Mailman
  • Published 2007
  • Biology, Medicine
  • Journal of Pharmacology and Experimental Therapeutics
  • The concept of intrinsic efficacy has been enshrined in pharmacology for half of a century, yet recent data have revealed that many ligands can differentially activate signaling pathways mediated via a single G protein-coupled receptor in a manner that challenges the traditional definition of intrinsic efficacy. Some terms for this phenomenon include functional selectivity, agonist-directed trafficking, and biased agonism. At the extreme, functionally selective ligands may be both agonists and… CONTINUE READING
    962 Citations

    Figures and Topics from this paper

    Functional Selectivity at Cannabinoid Receptors.
    • 15
    Ligand functional selectivity and quantitative pharmacology at G protein-coupled receptors
    • 58
    Making Sense of Pharmacology: Inverse Agonism and Functional Selectivity
    • K. Berg, W. P. Clarke
    • Chemistry, Medicine
    • The international journal of neuropsychopharmacology
    • 2018
    • 23
    • PDF
    A study of functional selectivity at the cannabinoid type 1 receptor
    • 1
    • Highly Influenced
    • PDF
    Functional Selectivity in Adrenergic and Angiotensin Signaling Systems
    • 57
    • PDF
    Missing Links: Mechanisms of Protean Agonism
    • R. Neubig
    • Chemistry, Medicine
    • Molecular Pharmacology
    • 2007
    • 33
    • PDF
    Functional Selectivity at Opioid Receptors
    • 1
    GPCR functional selectivity has therapeutic impact.
    • R. Mailman
    • Biology, Medicine
    • Trends in pharmacological sciences
    • 2007
    • 192
    • PDF
    Structure-functional selectivity relationship studies of β-arrestin-biased dopamine D₂ receptor agonists.
    • 94

    References

    SHOWING 1-10 OF 137 REFERENCES
    The elusive nature of intrinsic efficacy.
    • 100
    Functionally Different Agonists Induce Distinct Conformations in the G Protein Coupling Domain of the β2Adrenergic Receptor*
    • 336
    • PDF
    Hallucinogen actions on 5-HT receptors reveal distinct mechanisms of activation and signaling by G protein-coupled receptors
    • 33
    • PDF
    μ-Opioid Receptors: Ligand-Dependent Activation of Potassium Conductance, Desensitization, and Internalization
    • 167
    • PDF
    G Protein-Coupled Receptor Allosterism and Complexing
    • 820
    • PDF
    The structure and dynamics of GPCR oligomers: a new focus in models of cell-signaling mechanisms and drug design.
    • 33
    Probing the β2 Adrenoceptor Binding Site with Catechol Reveals Differences in Binding and Activation by Agonists and Partial Agonists*
    • 249
    • PDF