ReviewCanadian journal of anaesthesia = Journal canadien d'anesthesie2011
GABA(A) receptors as molecular targets of general anesthetics: identification of binding sites provides clues to allosteric modulation.
Review in Canadian journal of anaesthesia = Journal canadien d'anesthesie, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 2 of them syntheses that pooled it.
What it found
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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
46 citing papers in PubMed, 2 syntheses or guidelines pooled it, 113 citations in OpenAlex.
- Efficacy of Resveratrol in Experimental Subarachnoid Hemorrhage Animal Models: A Stratified Meta-Analysis.Frontiers in pharmacology · 2022Pooled it
- Efficacy of Melatonin in Animal Models of Subarachnoid Hemorrhage: A Systematic Review and Stratified Meta-Analysis.Frontiers in neurology · 2021Pooled it
- Functional role of translocator protein and its ligands in ocular diseases (Review).Molecular medicine reports · 2024Review
- Phenols and GABAFrontiers in pharmacology · 2024Review
- GABACell biology and toxicology · 2023Article
- A review of methods used to kill laboratory rodents: issues and opportunities.Laboratory animals · 2022Review
- Signatures of Thalamocortical Alpha Oscillations and Synchronization With Increased Anesthetic Depths Under Isoflurane.Frontiers in pharmacology · 2022Article
- Effects of General Anesthetics on Synaptic Transmission and Plasticity.Current neuropharmacology · 2022Review
- GABAIUPHAR/BPS guide to pharmacology CITE · 2021Article
- GABAJournal, genetic engineering & biotechnology · 2021Review
- Sodium pentobarbital dosages for exsanguination affect biochemical, molecular and histological measurements in rats.Scientific reports · 2020Article
- Review
- The Effects of General Anesthetics on Synaptic Transmission.Current neuropharmacology · 2020Review
- Identification of binding sites contributing to volatile anesthetic effects on GABA type A receptors.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- An allosteric propofol-binding site in kinesin disrupts kinesin-mediated processive movement on microtubules.The Journal of biological chemistry · 2018Article
- GABANeuropharmacology · 2018Review
- Metabolic Profiles of Propofol and Fospropofol: Clinical and Forensic Interpretative Aspects.BioMed research international · 2018Review
- Anesthetic Agents of Plant Origin: A Review of Phytochemicals with Anesthetic Activity.Molecules (Basel, Switzerland) · 2017Review
- Novel Molecule Exhibiting Selective Affinity for GABAScientific 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
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThe purpose of this review is to summarize current knowledge of detailed biochemical evidence for the role of γ-aminobutyric acid type A receptors (GABA(A)-Rs) in the mechanisms of general anesthesia. PRINCIPAL
findingsWith the knowledge that all general anesthetics positively modulate GABA(A)-R-mediated inhibitory transmission, site-directed mutagenesis comparing sequences of GABA(A)-R subunits of varying sensitivity led to identification of amino acid residues in the transmembrane domain that are critical for the drug actions in vitro. Using a photo incorporable analogue of the general anesthetic, R(+)etomidate, we identified two transmembrane amino acids that were affinity labelled in purified bovine brain GABA(A)-R. Homology protein structural modelling positions these two residues, αM1-11' and βM3-4', close to each other in a single type of intersubunit etomidate binding pocket at the β/α interface. This position would be appropriate for modulation of agonist channel gating. Overall, available information suggests that these two etomidate binding residues are allosterically coupled to sites of action of steroids, barbiturates, volatile agents, and propofol, but not alcohols. Residue α/βM2-15' is probably not a binding site but allosterically coupled to action of volatile agents, alcohols, and intravenous agents, and α/βM1-(-2') is coupled to action of intravenous agents.
conclusionsEstablishment of a coherent and consistent structural model of the GABA(A)-R lends support to the conclusion that general anesthetics can modulate function by binding to appropriate domains on the protein. Genetic engineering of mice with mutation in some of these GABA(A)-R residues are insensitive to general anesthetics in vivo, suggesting that further analysis of these domains could lead to development of more potent and specific drugs.
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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.