ReviewNaunyn-Schmiedeberg's archives of pharmacology2012
Clozapine, atypical antipsychotics, and the benefits of fast-off D2 dopamine receptor antagonism.
Review in Naunyn-Schmiedeberg's archives of pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 80 citations in OpenAlex.
- Amisulpride augmentation therapy improves cognitive performance and psychopathology in clozapine-resistant treatment-refractory schizophrenia: a 12-week randomized, double-blind, placebo-controlled trial.Military Medical Research · 2022Trial
- ADAPT-M: a workflow for rapid, quantitative in vitro measurements of enriched protein libraries.Nature communications · 2026Article
- A bibliometric study of the most-cited research articles and reviews in Naunyn-Schmiedeberg's Archives of Pharmacology (1969-2024).Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- ADAPT-M: A workflow for rapid, quantitativebioRxiv : the preprint server for biology · 2025Article
- The Effect of Antipsychotics on Cognition in Schizophrenia-A Current Narrative Review.Brain sciences · 2024Review
- Five-year trend of antipsychotic prescription practices in a district Hospital in Ghana: A retrospective study.Neuropsychopharmacology reports · 2023Article
- Article
- Adenosine AExperimental and therapeutic medicine · 2023Article
- Enhanced-Sampling Simulations for the Estimation of Ligand Binding Kinetics: Current Status and Perspective.Frontiers in molecular biosciences · 2022Review
- Distinct In Vitro Binding Profile of the Somatostatin Receptor Subtype 2 Antagonist [Pharmaceuticals (Basel, Switzerland) · 2021Article
- G protein signaling-biased mu opioid receptor agonists that produce sustained G protein activation are noncompetitive agonists.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- History of the dopamine hypothesis of antipsychotic action.World journal of psychiatry · 2021Review
- A structure-kinetic relationship study using matched molecular pair analysis.RSC medicinal chemistry · 2020Article
- On Calculating Free Energy Differences Using Ensembles of Transition Paths.Frontiers in molecular biosciences · 2020Article
- Binding kinetics of ligands acting at GPCRs.Molecular and cellular endocrinology · 2019Review
- In vitro and in silico analysis of the effects of DBritish journal of pharmacology · 2018Article
- Binding kinetics of cariprazine and aripiprazole at the dopamine DScientific reports · 2018Article
- Modelling the delay between pharmacokinetics and EEG effects of morphine in rats: binding kinetic versus effect compartment models.Journal of pharmacokinetics and pharmacodynamics · 2018Article
- Safety of antipsychotics for the treatment of schizophrenia: a focus on the adverse effects of clozapine.Therapeutic advances in drug safety · 2018Review
- Development of novel fluorescent histamine HScientific reports · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Drug-receptor interactions are traditionally quantified in terms of affinity and efficacy, but there is increasing awareness that the drug-on-receptor residence time also affects clinical performance. While most interest has hitherto been focused on slow-dissociating drugs, D(2) dopamine receptor antagonists show less extrapyramidal side effects but still have excellent antipsychotic activity when they dissociate swiftly. Fast dissociation of clozapine, the prototype of the "atypical antipsychotics", has been evidenced by distinct radioligand binding approaches both on cell membranes and intact cells. The surmountable nature of clozapine in functional assays with fast-emerging responses like calcium transients is confirmatory. Potential advantages and pitfalls of the hitherto used techniques are discussed, and recommendations are given to obtain more precise dissociation rates for such drugs. Surmountable antagonism is necessary to allow sufficient D(2) receptor stimulation by endogenous dopamine in the striatum. Simulations are presented to find out whether this can be achieved during sub-second bursts in dopamine concentration or rather during much slower, activity-related increases thereof. While the antagonist's dissociation rate is important to distinguish between both mechanisms, this becomes much less so when contemplating time intervals between successive drug intakes, i.e., when pharmacokinetic considerations prevail. Attention is also drawn to the divergent residence times of hydrophobic antagonists like haloperidol when comparing radioligand binding data on cell membranes with those on intact cells and clinical data.
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What OpenQuestion holds
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.