ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2016
Effects of β-Arrestin-Biased Dopamine D2 Receptor Ligands on Schizophrenia-Like Behavior in Hypoglutamatergic Mice.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 70 citations in OpenAlex.
- Biased Allosteric Modulation in GPCR Drug Discovery.Handbook of experimental pharmacology · 2026Review
- The clinical implication of β-arrestins-mediated signaling in memory and cognition.Molecular and cellular biochemistry · 2025Review
- Combination of Haloperidol With UNC9994, β-arrestin-Biased Analog of Aripiprazole, Ameliorates Schizophrenia-Related Phenotypes Induced by NMDAR Deficit in Mice.The international journal of neuropsychopharmacology · 2024Article
- Dopamine agonist Rotigotine mitigates lipopolysaccharide-induced neuroinflammation and memory impairment in mice.Metabolic brain disease · 2024Article
- Fluoroalkoxylated C-3 and C-9 (S)-12-bromostepholidine analogues with D1R antagonist activity.Bioorganic chemistry · 2023Article
- Understanding the Molecular Regulation of Serotonin Receptor 5-HTRJournal of molecular neuroscience : MN · 2023Article
- Dopamine Dynamics and Neurobiology of Non-Response to Antipsychotics, Relevance for Treatment Resistant Schizophrenia: A Systematic Review and Critical Appraisal.Biomedicines · 2023Review
- Intersection of the Orphan G Protein-Coupled Receptor, GPR19, with the Aging Process.International journal of molecular sciences · 2022Review
- Mechanisms Underlying Mu Opioid Receptor Effects on Parallel Fiber-Purkinje Cell Synaptic Transmission in Mouse Cerebellar Cortex.Frontiers in synaptic neuroscience · 2022Article
- LSD-stimulated behaviors in mice require β-arrestin 2 but not β-arrestin 1.Scientific reports · 2021Article
- New phosphosite-specific antibodies to unravel the role of GRK phosphorylation in dopamine DScientific reports · 2021Article
- Chirality of Novel Bitopic Agonists Determines Unique Pharmacology at the Dopamine D3 Receptor.Biomolecules · 2021Article
- Review
- Translation-Focused Approaches to GPCR Drug Discovery for Cognitive Impairments Associated with Schizophrenia.ACS pharmacology & translational science · 2020Review
- Assessment of Biased Agonism among Distinct Synthetic Cannabinoid Receptor Agonist Scaffolds.ACS pharmacology & translational science · 2020Article
- Dopamine Receptor Subtypes, Physiology and Pharmacology: New Ligands and Concepts in Schizophrenia.Frontiers in pharmacology · 2020Review
- Fine Tuning Muscarinic Acetylcholine Receptor Signaling Through Allostery and Bias.Frontiers in pharmacology · 2020Review
- Designing Functionally Selective Noncatechol Dopamine DACS chemical neuroscience · 2019Article
- Molecular pharmacology of metabotropic receptors targeted by neuropsychiatric drugs.Nature structural & molecular biology · 2019Review
- Utilization of Biased G Protein-Coupled ReceptorSignaling towards Development of Safer andPersonalized Therapeutics.Molecules (Basel, Switzerland) · 2019Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Current antipsychotic drugs (APDs) show efficacy with positive symptoms, but are limited in treating negative or cognitive features of schizophrenia. Whereas all currently FDA-approved medications target primarily the dopamine D2 receptor (D2R) to inhibit G(i/o)-mediated adenylyl cyclase, a recent study has shown that many APDs affect not only G(i/o)- but they can also influence β-arrestin- (βArr)-mediated signaling. The ability of ligands to differentially affect signaling through these pathways is termed functional selectivity. We have developed ligands that are devoid of D2R-mediated G(i/o) protein signaling, but are simultaneously partial agonists for D2R/βArr interactions. The purpose of this study was to test the effectiveness of UNC9975 or UNC9994 on schizophrenia-like behaviors in phencyclidine-treated or NR1-knockdown hypoglutamatergic mice. We have found the UNC compounds reduce hyperlocomotion in the open field, restore PPI, improve novel object recognition memory, partially normalize social behavior, decrease conditioned avoidance responding, and elicit a much lower level of catalepsy than haloperidol. These preclinical results suggest that exploitation of functional selectivity may provide unique opportunities to develop drugs with fewer side effects, greater therapeutic selectivity, and enhanced efficacy for treating schizophrenia and related conditions than medications that are currently available.
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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.