ArticleThe Journal of biological chemistry2019
The differential actions of clozapine and other antipsychotic drugs on the translocation of dopamine D2 receptors to the cell surface.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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, 2 syntheses or guidelines pooled it, 30 citations in OpenAlex.
- Is Aripiprazole an Effective Adjunct to Reduce Metabolic Adverse Effects Caused by Clozapine in Patients With Schizophrenia-A Systematic Review.Neuropsychopharmacology reports · 2026Pooled it
- Canonical and Non-Canonical Antipsychotics' Dopamine-Related Mechanisms of Present and Next Generation Molecules: A Systematic Review on Translational Highlights for Treatment Response and Treatment-Resistant Schizophrenia.International journal of molecular sciences · 2023Pooled it
- D3 dopamine receptors implicate a striatal neuronal subtype in the aversive effects of the antipsychotic drug quetiapine.bioRxiv : the preprint server for biology · 2026Article
- Pharmacological rescue of social deficits in rats featuring Disrupted-in-Schizophrenia-1 (DISC1) protein aggregation.Schizophrenia (Heidelberg, Germany) · 2026Article
- Second-generation antipsychotics - Cardiac ion channel modulation and QT interval disturbances: A review.Biomolecules & biomedicine · 2025Review
- Following the Action of Atypical Antipsychotic Clozapine and Possible Prediction of Treatment Response in Schizophrenia.Life (Basel, Switzerland) · 2025Review
- Deciphering complexity of GPCR signaling and modulation: implications and perspectives for drug discovery.Clinical science (London, England : 1979) · 2025Review
- Dysfunction of the NMDA Receptor in the Pathophysiology of Schizophrenia and/or the Pathomechanisms of Treatment-Resistant Schizophrenia.Biomolecules · 2024Review
- Pharmacological fingerprint of antipsychotic drugs at the serotonin 5-HTMolecular psychiatry · 2024Article
- Unique effect of clozapine on adenosine ABiomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023Article
- Dopamine Dynamics and Neurobiology of Non-Response to Antipsychotics, Relevance for Treatment Resistant Schizophrenia: A Systematic Review and Critical Appraisal.Biomedicines · 2023Review
- Article
- GPCRs in Intracellular Compartments: New Targets for Drug Discovery.Biomolecules · 2022Review
- Insights into the Promising Prospect of G Protein and GPCR-Mediated Signaling in Neuropathophysiology and Its Therapeutic Regulation.Oxidative medicine and cellular longevity · 2022Review
- Low-dose clozapine-related seizure: A case report and literature review.World journal of clinical cases · 2021Article
- The Antipsychotic Drug Clozapine Suppresses the RGS4 Polyubiquitylation and Proteasomal Degradation Mediated by the Arg/N-Degron Pathway.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Article
- A study of the structure-affinity relationship in SYA16263; is a DBioorganic & medicinal chemistry · 2021Article
- Successful rechallenge with paliperidone after clozapine treatment for a patient with dopamine supersensitivity psychosis.SAGE open medical case reports · 2020Article
- Residues and residue pairs of evolutionary importance differentially direct signaling bias of D2 dopamine receptors.The Journal of biological chemistry · 2019Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Most clinically available antipsychotic drugs (APDs) bind dopamine D2 receptors (D2R) at therapeutic concentrations, and it is thought that they suppress psychotic symptoms by serving as competitive antagonists of dopamine at D2R. Here, we present data that demonstrate that APDs act independently of dopamine at an intracellular pool of D2R to enhance transport of D2R to the cell surface and suggest that APDs can act as pharmacological chaperones at D2R. Among the first- and second-generation APDs that we tested, clozapine exhibited the lowest efficacy for translocating D2R to the cell surface. Thus, our observations could provide a cellular explanation for some of the distinct therapeutic characteristics of clozapine in schizophrenia. They also suggest that differential intracellular actions of APDs at their common G protein-coupled receptor (GPCR) target, D2R, could contribute to differences in their clinical profiles.
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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.