ArticleThe Journal of pharmacology and experimental therapeutics2015
Bias analyses of preclinical and clinical D2 dopamine ligands: studies with immediate and complex signaling pathways.
Article in The Journal of pharmacology and experimental therapeutics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 39 citations in OpenAlex.
- Apomorphine differentially engages the cAMP and β-arrestin signaling pathways relative to dopamine at human dopamine receptors.Journal of neural transmission (Vienna, Austria : 1996) · 2025Article
- Investigating the ligand agonism and antagonism at the DScientific reports · 2022Article
- Biased Ligands at the Kappa Opioid Receptor: Fine-Tuning Receptor Pharmacology.Handbook of experimental pharmacology · 2022Review
- G protein-coupled receptors: structure- and function-based drug discovery.Signal transduction and targeted therapy · 2021Review
- Pharmacological Insights Into Safety and Efficacy Determinants for the Development of Adenosine Receptor Biased Agonists in the Treatment of Heart Failure.Frontiers in pharmacology · 2021Article
- Discovery of Novel pERK1/2- or β-Arrestin-Preferring 5-HTJournal of medicinal chemistry · 2020Article
- A Review of the Therapeutic Potential of Recently Developed G Protein-Biased Kappa Agonists.Frontiers in pharmacology · 2019Review
- Current Concepts and Treatments of Schizophrenia.Molecules (Basel, Switzerland) · 2018Review
- Antipsychotic-Like Efficacy of Dopamine DMolecular neurobiology · 2018Article
- Signaling within Allosteric Machines: Signal Transmission Pathways Inside G Protein-Coupled Receptors.Molecules (Basel, Switzerland) · 2017Review
- Systematic errors in detecting biased agonism: Analysis of current methods and development of a new model-free approach.Scientific reports · 2017Article
- Identification of a selective small-molecule inhibitor of type 1 adenylyl cyclase activity with analgesic properties.Science signaling · 2017Article
- The Multiple Waves of Cannabinoid 1 Receptor Signaling.Molecular pharmacology · 2016Review
- Chronic constipation: improved understanding offers a new therapeutic approach.The Journal of physiology · 2016Article
- The β-Arrestins: Multifunctional Regulators of G Protein-coupled Receptors.The Journal of biological chemistry · 2016Review
- Biased ligand quantification in drug discovery: from theory to high throughput screening to identify new biased μ opioid receptor agonists.British journal of pharmacology · 2016Article
- Biased agonism: An emerging paradigm in GPCR drug discovery.Bioorganic & medicinal chemistry letters · 2016Review
- A commentary on the utility of a new L-DOPA-responsive dystonia mouse model.Rare diseases (Austin, Tex.) · 2016Article
- Gα(i/o)-coupled receptor-mediated sensitization of adenylyl cyclase: 40 years later.European journal of pharmacology · 2015Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
G protein-coupled receptors (GPCRs) often activate multiple signaling pathways, and ligands may evoke functional responses through individual pathways. These unique responses provide opportunities for biased or functionally selective ligands to preferentially modulate one signaling pathway over another. Studies with several GPCRs have suggested that selective activation of signaling pathways downstream of a GPCR may lead to safer and more effective drug therapies. The dopamine D2 receptor (D2R) is one of the main drug targets in the therapies for Parkinson's disease and schizophrenia. Recent studies suggest that selective modulation of individual signaling pathways downstream of the D2R may lead to safer antipsychotic drugs. In the present study, immediate effectors of the D2R (i.e., Gαi/o, Gβγ, β-arrestin recruitment) and more complex signaling pathways (i.e., extracellular signal-regulated kinase phosphorylation, heterologous sensitization, and dynamic mass redistribution) were examined in response to a series of D2R ligands. This was accomplished using Chinese hamster ovary cells stably expressing the human D2L dopamine receptor in the PathHunter β-Arrestin GPCR Assay Platform. The use of a uniform cellular background was designed to eliminate potential confounds associated with cell-to-cell variability, including expression levels of receptor as well as other components of signal transduction, including G protein subunits. Several well characterized and clinically relevant D2R ligands were evaluated across each signaling pathway in this cellular model. The most commonly used methods to measure ligand bias were compared. Functional selectivity analyses were also used as tools to explore the relative contribution of immediate D2R effectors for the activation of more complex signaling pathways.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.