ReviewDrug news & perspectives2010
The antipsychotic potential of muscarinic allosteric modulation.
Review in Drug news & perspectives, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 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
38 citing papers in PubMed, 67 citations in OpenAlex.
- Article
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- Discovery of Pre-Clinical CandidateACS chemical neuroscience · 2025Article
- Application of Deuterium in an MACS chemical neuroscience · 2025Article
- A New Era of Muscarinic Acetylcholine Receptor Modulators in Neurological Diseases, Cancer and Drug Abuse.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Discovery of VU0467319: an MACS chemical neuroscience · 2025Article
- Discovery of VU6016235: A Highly Selective, Orally Bioavailable, and Structurally Distinct Tricyclic MACS chemical neuroscience · 2024Article
- Discovery of VU6007496: Challenges in the Development of an MACS chemical neuroscience · 2024Article
- Discovery of VU6008677: A Structurally Distinct Tricyclic MACS medicinal chemistry letters · 2024Article
- Characterization of a Novel M4 PAM PET Radioligand [11C]PF06885190 in Nonhuman Primates (NHP).Molecules (Basel, Switzerland) · 2023Article
- Discovery of structurally distinct tricyclic MBioorganic & medicinal chemistry letters · 2021Article
- A Novel MACS chemical neuroscience · 2018Article
- VU6007477, a Novel MACS medicinal chemistry letters · 2018Article
- Discovery and Optimization of Potent and CNS Penetrant MACS chemical neuroscience · 2018Article
- Positive allosteric modulation of MNeuropharmacology · 2018Review
- Discovery of a novel 2,4-dimethylquinoline-6-carboxamide MBioorganic & medicinal chemistry letters · 2017Article
- Discovery of a novel, CNS penetrant MBioorganic & medicinal chemistry letters · 2017Article
- Diverse Effects on MACS chemical neuroscience · 2017Article
- Discovery of VU0467485/AZ13713945: An MACS medicinal chemistry letters · 2017Article
- Further optimization of the M1 PAM VU0453595: Discovery of novel heterobicyclic core motifs with improved CNS penetration.Bioorganic & medicinal chemistry letters · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The cholinergic hypothesis of schizophrenia emerged over 50 years ago based on clinical observations with both anticholinergics and pan-muscarinic agonists. Not until the 1990s did the cholinergic hypothesis of schizophrenia receive renewed enthusiasm based on clinical data with xanomeline, a muscarinic acetylcholine receptor M(1)/M(4)-preferring orthosteric agonist. In a clinical trial with Alzheimer's patients, xanomeline not only improved cognitive performance, but also reduced psychotic behaviors. This encouraging data spurred a second clinical trial in schizophrenic patients, wherein xanomeline significantly improved the positive, negative and cognitive symptom clusters. However, the question remained: Was the antipsychotic efficacy due to activation of M(1), M(4) or both M(1)/M(4)? Classical orthosteric ligands lacked the muscarinic receptor subtype selectivity required to address this key question. More recently, functional assays have allowed for the discovery of ligands that bind at allosteric sites, binding sites distinct from the orthosteric (acetylcholine) site, which are structurally less conserved and thereby afford high levels of receptor subtype selectivity. Recently, allosteric ligands, with unprecedented selectivity for either M(1) or M(4), have been discovered and have demonstrated comparable efficacy to xanomeline in preclinical antipsychotic and cognition models. These data suggest that selective allosteric activation of either M(1) or M(4) has antipsychotic potential through distinct, yet complimentary mechanisms.
Indexed as
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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.