ArticleNature2016
Crystal structures of the M1 and M4 muscarinic acetylcholine receptors.
Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 168 papers, 2 of them syntheses that pooled 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.
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
168 citing papers in PubMed, 2 syntheses or guidelines pooled it, 343 citations in OpenAlex.
- Is muscarinic receptor agonist effective and tolerant for schizophrenia?BMC psychiatry · 2025Pooled it
- Integrated meta-analysis, network pharmacology, and molecular docking to investigate the efficacy and potential pharmacological mechanism of Kai-Xin-San on Alzheimer's disease.Pharmaceutical biology · 2020Pooled it
- Trial
- Mapping Trofinetide Polypharmacology in Rett Syndrome: A Multi-Stage Computational Analysis.Journal of computational chemistry · 2026Article
- Next-generation chemogenetic inhibition using a brain-permeant non-prescription agent.Signal transduction and targeted therapy · 2026Article
- Development of a double-pharmacophore workflow for screening subtype-selective MMolecular diversity · 2026Article
- Cryptotanshinone as a Multi-Target Natural Terpenoid with Bronchodilator Potential: Insights from Integrated In Vitro and In Silico Studies.Molecules (Basel, Switzerland) · 2026Article
- Functional Evaluation of Tetrahydroisoquinoline-Derived Ligands Reveals Distinct Modulatory Profiles at the Muscarinic M1 Receptor.ACS medicinal chemistry letters · 2026Article
- From pharmacophore predictions to pharmaceutical possibilities: an integrated approach to screen MMolecular diversity · 2026Article
- Role of the neurotransmitter-receptor pathway in T-cell tumor immunology and cancer immunotherapy.Acta biochimica et biophysica Sinica · 2026Review
- A Meta-Analysis of In Vitro Release of Hydrophilic Therapeutics from Contact Lenses Using Mathematical Modeling.Pharmaceutics · 2025Article
- Ultra-large library screening with an evolutionary algorithm in Rosetta (REvoLd).Communications chemistry · 2025Article
- Bile Acids Are Potential Negative Allosteric Modulators of M1 Muscarinic Receptors.Biomolecules · 2025Article
- De novo design of a fusion protein tool for GPCR research.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Extracellular Peptide-Ligand Dimerization Actuator Receptor Design for Reversible and Spatially Dosed 3D Cell-Material Communication.ACS synthetic biology · 2025Article
- Visualizing agonist-induced M2 receptor activation regulated by aromatic ring dynamics.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A golden age of muscarinic acetylcholine receptor modulation in neurological diseases.Nature reviews. Drug discovery · 2024Review
- Positive allosteric modulation of a GPCR ternary complex.Science advances · 2024Article
- Entropy drives the ligand recognition in G-protein-coupled receptor subtypes.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Allosteric modulators of MScientific reports · 2024Article
108 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
Abstract
Muscarinic M1-M5 acetylcholine receptors are G-protein-coupled receptors that regulate many vital functions of the central and peripheral nervous systems. In particular, the M1 and M4 receptor subtypes have emerged as attractive drug targets for treatments of neurological disorders, such as Alzheimer's disease and schizophrenia, but the high conservation of the acetylcholine-binding pocket has spurred current research into targeting allosteric sites on these receptors. Here we report the crystal structures of the M1 and M4 muscarinic receptors bound to the inverse agonist, tiotropium. Comparison of these structures with each other, as well as with the previously reported M2 and M3 receptor structures, reveals differences in the orthosteric and allosteric binding sites that contribute to a role in drug selectivity at this important receptor family. We also report identification of a cluster of residues that form a network linking the orthosteric and allosteric sites of the M4 receptor, which provides new insight into how allosteric modulation may be transmitted between the two spatially distinct domains.
Indexed as
Identifiers
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.