Proposed therapeutic applications of functional selectivity and biased signaling

Thyroid-stimulating hormoneActivation Gaq>>GαsSelective thyroid hormone synthesisVassart and Dumont (1992)
β-AdrenoceptorActivation Gas>>Gα1Treatment of congestive heart failureShizudu and Buttrick (2002)
Histamine↑cAMP >>allergic responseNeuropsychiatric/neurodegenerative disordersGaleotti et al. (2004)
GPR109Gαi >> β-arrestin activation↓ Triglycerides with no cutaneous flushingWalters et al. (2009); Richman et al. (2008)
α2-Adrenoceptor↓ β-Arrestin activationHypotension with reduced sedationSchmid and Bohn (2009)
Dopamine D2↓ Mitogen-activated protein kinase phosphorylation + ↓ internalizationImproved profile for treatment of schizophreniaGrady et al. (2003); Urban et al. (2007)
PTHSelective β-arrestin activationImproved treatment of osteoporosisGesty-Palmer et al. (2009); Schmid et al. (2008)
Opioid↓ β-Arrestin interactionAnalgesia with ↓tolerance/↓respiratory depression/↓constipationXu et al. (2007); Bohn et al. (1999); Groer et al. (2007)
Dopamine D1↓ InternalizationImproved therapy for ParkinsonRyman-Rasmussen et al. (2007)
Angiotensin↑ β-Arrestin activation/↓ G protein activationAntihypertensive therapy with antiapoptitic effectWei et al. (2003); Rajagopla et al. (2005); Violin and Lefkowitz (2007)
Angiotensin↑ β-Arrestin activation/↓ G protein activationAntihypertensive effect with cardioprotectionZhai et al. (2005); Rajagopal et al. (2006); Aplin et al. (2009)
5-Hydroxytryptamine↓ Interaction with PTENTreatment of addictionJi et al. (2006)
Gastrin-releasing peptide/Arg vasopressinReceptor blockade + ERK stimulationTreatment of small-cell lung cancerMacKinnon et al. (2005)
β-AdrenoceptorReceptor blockade + ERK stimulationImproved treatment of congestive heart failureMetra et al. (2004); Wisler et al. (2007)
Many overexpressed seven-transmembrane receptors↑ Receptor internalizationNumerous cancersBosier and Hermans (2007)
5-Hydroxytryptamine↑ Receptor internalizationTreatment of psychosis/depressionWillins et al. (1999)