Evidence map›Paper›PMID 19909227›Full record

ReviewCurrent pharmaceutical design2010

Third generation antipsychotic drugs: partial agonism or receptor functional selectivity?

Richard B Mailman, Vishakantha Murthy

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Current pharmaceutical design, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 123 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
123citing papers in PubMed, 2 pooled it
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

123 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. "Efficacy, safety and certainty of evidence for selective D1/D5 dopamine receptor partial agonists in Parkinson's disease: a systematic review, meta-analysis and GRADE assessment".Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026
    Pooled it
  2. Pooled it
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  15. Advances in Mood Disorder Pharmacotherapy: Evaluating New Antipsychotics and Mood Stabilizers for Bipolar Disorder and Schizophrenia.Medical science monitor : international medical journal of experimental and clinical research · 2024
    Review
  16. Exploring causal mechanisms of psychosis risk.Neuroscience and biobehavioral reviews · 2024
    Review
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63 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors.

Richard B MailmanPenn State University College of Medicine - Milton S. Hershey Medical Center Department of Pharmacology. R130 500 University Dr., PO Box 850, Hershey, PA 17033-0850, USA. rmailman@psu.edu
Vishakantha Murthy

Funding

Screening CoreU19MH082441 · NIMH · UNIV OF NORTH CAROLINA CHAPEL HILL · PI CARON, MARC G., JIN, JIAN · 2007 to 2016
$15.2M
NOVEL MOLECULAR SITE FOR ANTIDOPAMINERGIC EFFECTSR01MH040537 · NIMH · UNIVERSITY OF NORTH CAROLINA CHAPEL HILL · PI MAILMAN, RICHARD B · 1985 to 2001
$506k
NIMH NIH HHS MH040537NIMH NIH HHS MH082441NIMH NIH HHS R01 MH040537NIMH NIH HHS U19 MH082441
6 · The paper itself

Abstract

Functional selectivity is the term that describes drugs that cause markedly different signaling through a single receptor (e.g., full agonist at one pathway and antagonist at a second). It has been widely recognized recently that this phenomenon impacts the understanding of mechanism of action of some drugs, and has relevance to drug discovery. One of the clinical areas where this mechanism has particular importance is in the treatment of schizophrenia. Antipsychotic drugs have been grouped according to both pattern of clinical action and mechanism of action. The original antipsychotic drugs such as chlorpromazine and haloperidol have been called typical or first generation. They cause both antipsychotic actions and many side effects (extrapyramidal and endocrine) that are ascribed to their high affinity dopamine D(2) receptor antagonism. Drugs such as clozapine, olanzapine, risperidone and others were then developed that avoided the neurological side effects (atypical or second generation antipsychotics). These compounds are divided mechanistically into those that are high affinity D(2) and 5-HT(2A) antagonists, and those that also bind with modest affinity to D(2), 5-HT(2A), and many other neuroreceptors. There is one approved third generation drug, aripiprazole, whose actions have been ascribed alternately to either D(2) partial agonism or D(2) functional selectivity. Although partial agonism has been the more widely accepted mechanism, the available data are inconsistent with this mechanism. Conversely, the D(2) functional selectivity hypothesis can accommodate all current data for aripiprazole, and also impacts on discovery compounds that are not pure D(2) antagonists.

Indexed as

Dopamine D2 Receptor AntagonistsDrug Partial AgonismAnimalsAntipsychotic AgentsAripiprazoleDrug DiscoveryDrugs, InvestigationalHumansModels, NeurologicalMolecular StructurePiperazinesQuinolonesReceptors, Dopamine D2Serotonin AntagonistsSignal TransductionTerminology as TopicAntipsychotic AgentsAripiprazoleDopamine D2 Receptor AntagonistsDrugs, InvestigationalPiperazinesQuinolonesReceptors, Dopamine D2Serotonin Antagonists

Identifiers

PMID19909227
PMCPMC2958217

What OpenQuestion holds

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Registered trials

None linked

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.