ArticleThe Journal of biological chemistry2011
Molecular determinants of ivermectin sensitivity at the glycine receptor chloride channel.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 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
34 citing papers in PubMed, 63 citations in OpenAlex.
- Structural basis for domain coupling in heteromeric glycine receptors revealed by an atypical allosteric agonist.Science advances · 2026Article
- Lethal effects of ivermectin structures on malaria vectors and in silico analysis of interactions with their glutamate-gated chloride ion channels.Scientific reports · 2026Article
- Article
- Allosteric Cholesterol Site in Glycine Receptors Characterized through Molecular Simulations.The journal of physical chemistry. B · 2024Article
- Conformational transitions and allosteric modulation in a heteromeric glycine receptor.Nature communications · 2023Article
- Modulation of P2XPhysiological reports · 2022Article
- Positive Allosteric Modulators of Glycine Receptors and Their Potential Use in Pain Therapies.Pharmacological reviews · 2022Review
- Potential therapeutic effects of Ivermectin in COVID-19.Experimental biology and medicine (Maywood, N.J.) · 2022Article
- Chemogenetics as a neuromodulatory approach to treating neuropsychiatric diseases and disorders.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Review
- Anti-inflammatory activity of ivermectin in late-stage COVID-19 may reflect activation of systemic glycine receptors.Open heart · 2021Article
- Nematicidal and insecticidal activities of halogenated indoles.Scientific reports · 2019Article
- Fitness costs of key point mutations that underlie acaricide target-site resistance in the two-spotted spider miteEvolutionary applications · 2018Article
- Chemogenetic Tools for Causal Cellular and Neuronal Biology.Physiological reviews · 2018Review
- Effects of glutamate and ivermectin on single glutamate-gated chloride channels of the parasitic nematode H. contortus.PLoS pathogens · 2017Article
- Trapping of ivermectin by a pentameric ligand-gated ion channel upon open-to-closed isomerization.Scientific reports · 2017Article
- Mutational Analysis at Intersubunit Interfaces of an Anionic Glutamate Receptor Reveals a Key Interaction Important for Channel Gating by Ivermectin.Frontiers in molecular neuroscience · 2017Article
- Voltage-Dependent Inhibition of Glycine Receptor Channels by Niflumic Acid.Frontiers in molecular neuroscience · 2017Article
- Membrane potential depolarization causes alterations in neuron arrangement and connectivity in cocultures.Brain and behavior · 2015Article
- Functional characterization of ivermectin binding sites in α1β2γ2L GABA(A) receptors.Frontiers in molecular neuroscience · 2015Article
- Recent advances in candidate-gene and whole-genome approaches to the discovery of anthelmintic resistance markers and the description of drug/receptor interactions.International journal for parasitology. Drugs and drug resistance · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ivermectin is an anthelmintic drug that works by activating glutamate-gated chloride channel receptors (GluClRs) in nematode parasites. GluClRs belong to the Cys-loop receptor family that also includes glycine receptor (GlyR) chloride channels. GluClRs and A288G mutant GlyRs are both activated by low nanomolar ivermectin concentrations. The crystal structure of the Caenorhabditis elegans α GluClR complexed with ivermectin has recently been published. Here, we probed ivermectin sensitivity determinants on the α1 GlyR using site-directed mutagenesis and electrophysiology. Based on a mutagenesis screen of transmembrane residues, we identified Ala288 and Pro230 as crucial sensitivity determinants. A comparison of the actions of selamectin and ivermectin suggested the benzofuran C05-OH was required for high efficacy. When taken together with docking simulations, these results supported a GlyR ivermectin binding orientation similar to that seen in the GluClR crystal structure. However, whereas the crystal structure shows that ivermectin interacts with the α GluClR via H-bonds with Leu218, Ser260, and Thr285 (α GluClR numbering), our data indicate that H-bonds with residues homologous to Ser260 and Thr285 are not important for high ivermectin sensitivity or direct agonist efficacy in A288G α1 GlyRs or three other GluClRs. Our data also suggest that van der Waals interactions between the ivermectin disaccharide and GlyR M2-M3 loop residues are unimportant for high ivermectin sensitivity. Thus, although our results corroborate the ivermectin binding orientation as revealed by the crystal structure, they demonstrate that some of the binding interactions revealed by this structure do not pertain to other highly ivermectin-sensitive Cys-loop receptors.
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.