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In Vivo Evidence for and Consequences of Functional Selectivity

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Functional Selectivity of G Protein-Coupled Receptor Ligands

Part of the book series: The Receptors ((REC))

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Abstract

Functional selectivity refers to the ability of some ligands to stimulate a subset of the possible consequences of activation of a receptor. This chapter addresses two related issues that are critical for consideration of the therapeutic utility of functional selectivity: the evidence that functional selectivity is a pharmacologically relevant phenomenon that can be observed in vivo, and characterization of the unique in vivo properties of functionally selective ligands. Topics reviewed include G protein-biased agonists for μ-opioid and serotonin 5-HT2A receptors, arrestin-biased agonists for angiotensin II AT1 receptors and β - adrenergic receptors, antagonists that cause internalization of 5-HT2A receptors, and in vivo evidence for functionally selective dopamine receptor ligands. Barriers to using functional selectivity as a criterion for rational drug design are discussed.

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  1. CRULRG, Research Institute, Université Laval, Quebec City, Canada

    Kim A. Neve, Marc G. Caron & Jean-Martin Beaulieu

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  1. Kim A. Neve
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  1. VA Medical Center, 3710 SW US Veterans Hospital Road, 97239-2999, Portland, OR, USA

    Kim A. Neve

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Neve, K.A., Caron, M.G., Beaulieu, JM. (2009). In Vivo Evidence for and Consequences of Functional Selectivity. In: Neve, K.A. (eds) Functional Selectivity of G Protein-Coupled Receptor Ligands. The Receptors. Humana Press. https://doi.org/10.1007/978-1-60327-335-0_6

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