ArticleNeuropharmacology2011
Competitive binding at a nicotinic receptor transmembrane site of two α7-selective positive allosteric modulators with differing effects on agonist-evoked desensitization.
Article in Neuropharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 60 citations in OpenAlex.
- Effects of ivermectin on the activation and desensitization of the human GABAMolecular pharmacology · 2026Article
- Drug Discovery Targeting Nicotinic Acetylcholine Receptors for Hearing Loss.International journal of molecular sciences · 2026Review
- Development of a novel alpha7-nicotinic acetylcholine receptor-selective cell-penetrating peptide for intracellular cargo transport.Drug delivery · 2025Article
- Structural basis for allosteric agonism of human α7 nicotinic acetylcholine receptors.Cell discovery · 2025Article
- Symmetrical Bispyridinium Compounds Act as Open Channel Blockers of Cation-Selective Ion Channels.ACS pharmacology & translational science · 2024Article
- Article
- Modulation of the mammalian GABABritish journal of pharmacology · 2022Article
- The α9α10 nicotinic acetylcholine receptor: a compelling drug target for hearing loss?Expert opinion on therapeutic targets · 2022Review
- Nicotinic receptor pharmacology in silico: Insights and challenges.Neuropharmacology · 2020Review
- In Silico Modeling of the α7 Nicotinic Acetylcholine Receptor: New Pharmacological Challenges Associated with Multiple Modes of Signaling.Mini reviews in medicinal chemistry · 2020Review
- Quantitative assessment of oligomeric amyloid β peptide binding to α7 nicotinic receptor.British journal of pharmacology · 2019Article
- Article
- An allosteric binding site of the α7 nicotinic acetylcholine receptor revealed in a humanized acetylcholine-binding protein.The Journal of biological chemistry · 2018Article
- Diversity of Nicotinic Acetylcholine Receptor Positive Allosteric Modulators Revealed by Mutagenesis and a Revised Structural Model.Molecular pharmacology · 2018Article
- Trapping of ivermectin by a pentameric ligand-gated ion channel upon open-to-closed isomerization.Scientific reports · 2017Article
- Calcium imaging with genetically encoded sensor Case12: Facile analysis of α7/α9 nAChR mutants.PloS one · 2017Article
- The influence of allosteric modulators and transmembrane mutations on desensitisation and activation of α7 nicotinic acetylcholine receptors.Neuropharmacology · 2015Article
- An Unaltered Orthosteric Site and a Network of Long-Range Allosteric Interactions for PNU-120596 in α7 Nicotinic Acetylcholine Receptors.Chemistry & biology · 2015Article
- Review
- 6-bromohypaphorine from marine nudibranch mollusk Hermissenda crassicornis is an agonist of human α7 nicotinic acetylcholine receptor.Marine drugs · 2015Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Positive allosteric modulators (PAMs) of nicotinic acetylcholine receptors (nAChRs) have attracted considerable interest as a novel area of therapeutic drug discovery. Two types of α7-selective PAMs have been identified (type I and type II). Whilst both potentiate peak agonist-induced responses, they have different effects on the rate of agonist-induced receptor desensitization. Type I PAMs have little or no effect on the rapid rate of desensitization that is characteristic of α7 nAChRs, whereas type II PAMs cause dramatic slowing of receptor desensitization. Previously, we have obtained evidence indicating that PNU-120596, a type II PAM, causes potentiation by interacting with an allosteric transmembrane site. In contrast, other studies have demonstrated the importance of the 'M2-M3 segment' in modulating the effects of the type I PAM NS1738 and have led to the proposal that NS1738 may interact with the extracellular N-terminal domain. Here, our aim has been to compare the mechanism of allosteric potentiation of α7 nAChRs by NS1738 and PNU-120596. Functional characterization of a series of mutated α7 nAChRs indicates that mutation of amino acids within a proposed intrasubunit transmembrane cavity have a broadly similar effect on these two PAMs. In addition, we have employed a functional assay designed to examine the ability of ligands to act competitively at either the orthosteric or allosteric binding site of α7 nAChRs. These data, together with computer docking simulations, lead us to conclude that both the type I PAM NS1738 and the type II PAM PNU-120596 bind competitively at a mutually exclusive intrasubunit transmembrane site.
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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.