Evidence map›Paper›PMID 21956443›Full record

ReviewNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2012

Muscarinic and nicotinic acetylcholine receptor agonists and allosteric modulators for the treatment of schizophrenia.

Carrie K Jones, Nellie Byun, Michael Bubser

Abstract readReview
In one paragraph

Review in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
103citing papers in PubMed, 3 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

103 citing papers in PubMed, 3 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Trial
  5. Review
  6. Article
  7. Novel drug treatments for schizophrenia.Nature reviews. Drug discovery · 2026
    Review
  8. Article
  9. Cholinergic system in patients with chronic kidney disease: cognitive and renal implications.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025
    Review
  10. Behavioral Changes inJournal of clinical medicine · 2025
    Article
  11. Review
  12. Article
  13. Discovery of Pre-Clinical CandidateACS chemical neuroscience · 2025
    Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

43 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

3 authors.

Carrie K JonesVanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232, USA. carrie.jones@vanderbilt.edu
Nellie Byun
Michael Bubser

Funding

Postdoctoral Training in Biomedical MRI and MRST32EB001628 · NIBIB · VANDERBILT UNIVERSITY MEDICAL CENTER · PI John C Gore · 2003 to 2026
$7.0M
M4 Positive Allosteric Modulators for the Treatment of SchizophreniaR01MH086601 · NIMH · VANDERBILT UNIVERSITY · PI JONES, CARRIE KIMBERLY · 2009 to 2013
$1.9M
NIBIB NIH HHS T32 EB001628NIMH NIH HHS R01 MH086601
6 · The paper itself

Abstract

Muscarinic and nicotinic acetylcholine (ACh) receptors (mAChRs and nAChRs) are emerging as important targets for the development of novel treatments for the symptoms associated with schizophrenia. Preclinical and early proof-of-concept clinical studies have provided strong evidence that activators of specific mAChR (M(1) and M(4)) and nAChR (α(7) and α(2)β(4)) subtypes are effective in animal models of antipsychotic-like activity and/or cognitive enhancement, and in the treatment of positive and cognitive symptoms in patients with schizophrenia. While early attempts to develop selective mAChR and nAChR agonists provided important preliminary findings, these compounds have ultimately failed in clinical development due to a lack of true subtype selectivity and subsequent dose-limiting adverse effects. In recent years, there have been major advances in the discovery of highly selective activators for the different mAChR and nAChR subtypes with suitable properties for optimization as potential candidates for clinical trials. One novel strategy has been to identify ligands that activate a specific receptor subtype through actions at sites that are distinct from the highly conserved ACh-binding site, termed allosteric sites. These allosteric activators, both allosteric agonists and positive allosteric modulators, of mAChR and nAChR subtypes demonstrate unique mechanisms of action and high selectivity in vivo, and may provide innovative treatment strategies for schizophrenia.

Indexed as

Allosteric RegulationDrug DesignHumansMuscarinic AgonistsNicotinic AgonistsSchizophreniaMuscarinic AgonistsNicotinic Agonists

Identifiers

PMID21956443
PMCPMC3238081

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.