ArticlePloS one2016
The Novel, Nicotinic Alpha7 Receptor Partial Agonist, BMS-933043, Improves Cognition and Sensory Processing in Preclinical Models of Schizophrenia.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis 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
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Cognitive Enhancers in Schizophrenia: A Systematic Review and Meta-Analysis of Alpha-7 Nicotinic Acetylcholine Receptor Agonists for Cognitive Deficits and Negative Symptoms.Frontiers in psychiatry · 2021Pooled it
- Efficacy and safety of an alpha 7-nicotinic acetylcholine receptor agonist, VQW-765, in subjects with performance anxiety: randomised, double-blind, placebo-controlled trial.The British journal of psychiatry : the journal of mental science · 2025Trial
- Investigation of varenicline and tropisetron in latent inhibition and novel object recognition in mice.Scientific reports · 2026Article
- Neutral or Detrimental Effects of TREM2 Agonist Antibodies in Preclinical Models of Alzheimer's Disease and Multiple Sclerosis.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- A phase 1b/2a multicenter study of the safety and preliminary pharmacodynamic effects of selective muscarinic MAlzheimer's & dementia (New York, N. Y.) · 2022Article
- Cognitive Deficit in Schizophrenia: From Etiology to Novel Treatments.International journal of molecular sciences · 2021Review
- Mismatch negativity as EEG biomarker supporting CNS drug development: a transnosographic and translational study.Translational psychiatry · 2021Article
- Therapeutic potential of α7 nicotinic acetylcholine receptor agonists to combat obesity, diabetes, and inflammation.Reviews in endocrine & metabolic disorders · 2020Review
- α7 nicotinic acetylcholine receptors as therapeutic targets in schizophrenia: Update on animal and clinical studies and strategies for the future.Neuropharmacology · 2020Review
- The spinal microglial IL-10/β-endorphin pathway accounts for cinobufagin-induced mechanical antiallodynia in bone cancer pain following activation of α7-nicotinic acetylcholine receptors.Journal of neuroinflammation · 2020Article
- Improving Effects of Hop-Derived Bitter Acids in Beer on Cognitive Functions: A New Strategy for Vagus Nerve Stimulation.Biomolecules · 2020Review
- Cortical Microcircuit Mechanisms of Mismatch Negativity and Its Underlying Subcomponents.Frontiers in neural circuits · 2020Review
- Pharmacological characterization of JWX-A0108 as a novel type I positive allosteric modulator of α7 nAChR that can reverse acoustic gating deficits in a mouse prepulse inhibition model.Acta pharmacologica Sinica · 2019Article
- Nicotinic Acetylcholine Receptor Ligands, Cognitive Function, and Preclinical Approaches to Drug Discovery.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2019Review
- Schizophrenia: synthetic strategies and recent advances in drug design.MedChemComm · 2018Review
- The current agonists and positive allosteric modulators ofActa pharmaceutica Sinica. B · 2017Review
- BMS-933043, a Selective α7 nAChR Partial Agonist for the Treatment of Cognitive Deficits Associated with Schizophrenia.ACS medicinal chemistry letters · 2017Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
23 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The development of alpha7 nicotinic acetylcholine receptor agonists is considered a promising approach for the treatment of cognitive symptoms in schizophrenia patients. In the present studies we characterized the novel agent, (2R)-N-(6-(1H-imidazol-1-yl)-4-pyrimidinyl)-4'H-spiro[4-azabicyclo[2.2.2]octane-2,5'-[1,3]oxazol]-2'-amine (BMS-933043), in vitro and in rodent models of schizophrenia-like deficits in cognition and sensory processing. BMS-933043 showed potent binding affinity to native rat (Ki = 3.3 nM) and recombinant human alpha7 nicotinic acetylcholine receptors (Ki = 8.1 nM) and agonist activity in a calcium fluorescence assay (EC50 = 23.4 nM) and whole cell voltage clamp electrophysiology (EC50 = 0.14 micromolar (rat) and 0.29 micromolar (human)). BMS-933043 exhibited a partial agonist profile relative to acetylcholine; the relative efficacy for net charge crossing the cell membrane was 67% and 78% at rat and human alpha7 nicotinic acetylcholine receptors respectively. BMS-933043 showed no agonist or antagonist activity at other nicotinic acetylcholine receptor subtypes and was at least 300 fold weaker at binding to and antagonizing human 5-HT3A receptors (Ki = 2,451 nM; IC50 = 8,066 nM). BMS-933043 treatment i) improved 24 hour novel object recognition memory in mice (0.1-10 mg/kg, sc), ii) reversed MK-801-induced deficits in Y maze performance in mice (1-10 mg/kg, sc) and set shift performance in rats (1-10 mg/kg, po) and iii) reduced the number of trials required to complete the extradimensional shift discrimination in neonatal PCP treated rats performing the intra-dimensional/extradimensional set shifting task (0.1-3 mg/kg, po). BMS-933043 also improved auditory gating (0.56-3 mg/kg, sc) and mismatch negativity (0.03-3 mg/kg, sc) in rats treated with S(+)ketamine or neonatal phencyclidine respectively. Given this favorable preclinical profile BMS-933043 was selected for further development to support clinical evaluation in humans.
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.