ArticleBritish journal of pharmacology2012
Augmentation of cognitive function by NS9283, a stoichiometry-dependent positive allosteric modulator of α2- and α4-containing nicotinic acetylcholine receptors.
Article in British journal of pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 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
61 citing papers in PubMed, 104 citations in OpenAlex.
- Targeted Mutations Activate Allosteric Modulation of α5-Containing Nicotinic Acetylcholine Receptors.ACS chemical neuroscience · 2026Article
- The Human Alpha3 Beta2 Neuronal Nicotinic Acetylcholine Receptor Can Form Two Distinguishable Subtypes.International journal of molecular sciences · 2025Article
- A Pharmacophore for Drugs Targeting the α4α4 Binding Site of the (α4)Journal of neurochemistry · 2025Article
- Enhanced prefrontal nicotinic signaling as evidence of active compensation in Alzheimer's disease models.Translational neurodegeneration · 2024Article
- Enhanced Novel Object Recognition and Spatial Memory in Rats Selectively Bred for High Nicotine Preference.Brain sciences · 2024Article
- SR9883 is a novel small-molecule enhancer of α4β2* nicotinic acetylcholine receptor signaling that decreases intravenous nicotine self-administration in rats.Frontiers in molecular neuroscience · 2024Article
- Recent Advances in the Discovery of Nicotinic Acetylcholine Receptor Allosteric Modulators.Molecules (Basel, Switzerland) · 2023Review
- Stoichiometry-Selective Antagonism of α4β2 Nicotinic Acetylcholine Receptors by Fluoroquinolone Antibiotics.ACS chemical neuroscience · 2022Article
- Neurobiological Mechanisms of Nicotine Reward and Aversion.Pharmacological reviews · 2022Review
- Stable desensitization of αEuropean journal of pharmacology · 2021Article
- Novel Putative Positive Modulators of α4β2 nAChRs Potentiate Nicotine Reward-Related Behavior.Molecules (Basel, Switzerland) · 2021Article
- Potentiation of (α4)2(β2)3, but not (α4)3(β2)2, nicotinic acetylcholine receptors reduces nicotine self-administration and withdrawal symptoms.Neuropharmacology · 2021Article
- NACHO and 14-3-3 promote expression of distinct subunit stoichiometries of the α4β2 acetylcholine receptor.Cellular and molecular life sciences : CMLS · 2021Article
- Allosterically PotentiatedMolecular pharmacology · 2020Article
- Article
- Heterologous expression of concatenated nicotinic ACh receptors: Pros and cons of subunit concatenation and recommendations for construct designs.British journal of pharmacology · 2020Article
- Allosterism of Nicotinic Acetylcholine Receptors: Therapeutic Potential for Neuroinflammation Underlying Brain Trauma and Degenerative Disorders.International journal of molecular sciences · 2020Review
- Activation of Somatostatin Interneurons by Nicotinic Modulator Lypd6 Enhances Plasticity and Functional Recovery in the Adult Mouse Visual Cortex.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Desformylflustrabromine, a positive allosteric modulator of α4β2-containing nicotinic acetylcholine receptors, enhances cognition in rats.Pharmacological reports : PR · 2020Article
- Development of novelRSC advances · 2020Article
1 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
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposePositive allosteric modulation of α4β2 nicotinic acetylcholine (nACh) receptors could add a new dimension to the pharmacology and therapeutic approach to these receptors. The novel modulator NS9283 was therefore tested extensively. EXPERIMENTAL APPROACH: Effects of NS9283 were evaluated in vitro using fluorescence-based Ca(2+) imaging and electrophysiological voltage clamp experiments in Xenopus oocytes, mammalian cells and thalamocortical neurons. In vivo the compound was tested in models covering a range of cognitive domains in mice and rats. KEY
resultsNS9283 was shown to increase agonist-evoked response amplitude of (α4)(3) (β2)(2) nACh receptors in electrophysiology paradigms. (α2)(3) (β2)(2) , (α2)(3) (β4)(2) and (α4)(3) (β4)(2) were modulated to comparable extents, but no effects were detected at α3-containing or any 2α : 3β stoichiometry nACh receptors. Native nACh receptors in thalamocortical neurons similarly displayed DHβE-sensitive currents that were receptive to modulation. NS9283 had favourable effects on sensory information processing, as shown by reversal of PCP-disrupted pre-pulse inhibition. NS9283 further improved performance in a rat model of episodic memory (social recognition), a rat model of sustained attention (five-choice serial reaction time task) and a rat model of reference memory (Morris water maze). Importantly, the effects in the Morris water maze could be fully reversed with mecamylamine, a blocker of nACh receptors. CONCLUSIONS AND IMPLICATIONS: These results provide compelling evidence that positive allosteric modulators acting at the (α4)(3) (β2)(2) nACh receptors can augment activity across a broad range of cognitive domains, and that α4β2 nACh receptor allosteric modulation therefore constitutes a promising therapeutic approach to symptomatic treatment of cognitive impairment.
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.