Evidence map›Paper›PMID 24912155›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2014

GABAA receptor target of tetramethylenedisulfotetramine.

Chunqing Zhao, Sung Hee Hwang, Bruce A Buchholz, Timothy S Carpenter, Felice C Lightstone, Felice Lightstone, Jun Yang, Bruce D Hammock, John E Casida

Erratum issuedOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
5.3field-weighted citation impact, top 5% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

32 citing papers in PubMed, 53 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. The efficacy of γ-aminobutyric acid type A receptor (GABAToxicology and applied pharmacology · 2021
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Humulone Modulation of GABAFrontiers in neuroscience · 2020
    Article
  13. Review
  14. Nutrients · 2019
    Article
  15. Vitamin B12 Added as a Fortificant to Flour Retains High Bioavailability when Baked in Bread.Nuclear instruments & methods in physics research. Section B, Beam interactions with materials and atoms · 2019
    Article
  16. Naphthalene DNA Adduct Formation and Tolerance in the Lung.Nuclear instruments & methods in physics research. Section B, Beam interactions with materials and atoms · 2019
    Article
  17. Article
  18. Article
  19. Review
  20. GABANeuropharmacology · 2018
    Review
4 · The record

Corrections and comments

  • Erratum issued
    Lightstone, Felice [corrected to Lightstone, Felice C]
5 · Who and what money

Authors and funding

9 authors at 3 institutions in 1 country.

Chunqing ZhaoEnvironmental Chemistry and Toxicology Laboratory, Department of Environmental Science, Policy, and Management, University of California, Berkeley, CA 94720;
Sung Hee HwangDepartment of Entomology, College of Agricultural and Environmental Science, University of California, Davis, CA 95616; and.
Bruce A BuchholzCenter for Accelerator Mass Spectrometry and buchholz2@llnl.gov lightstone1@llnl.gov bdhammock@ucdavis.edu ectl@berkeley.edu.
Timothy S CarpenterBiosciences and Biotechnology Division, Lawrence Livermore National Laboratory, Livermore, CA 94551.
Felice C Lightstone
Felice LightstoneBiosciences and Biotechnology Division, Lawrence Livermore National Laboratory, Livermore, CA 94551 buchholz2@llnl.gov lightstone1@llnl.gov bdhammock@ucdavis.edu ectl@berkeley.edu.
Jun YangDepartment of Entomology, College of Agricultural and Environmental Science, University of California, Davis, CA 95616; and.
Bruce D HammockDepartment of Entomology, College of Agricultural and Environmental Science, University of California, Davis, CA 95616; and buchholz2@llnl.gov lightstone1@llnl.gov bdhammock@ucdavis.edu ectl@berkeley.edu.
John E CasidaEnvironmental Chemistry and Toxicology Laboratory, Department of Environmental Science, Policy, and Management, University of California, Berkeley, CA 94720; buchholz2@llnl.gov lightstone1@llnl.gov bdhammock@ucdavis.edu ectl@berkeley.edu.
University of California, Davis · USLawrence Livermore National Laboratory · USUniversity of California, Berkeley · US

Funding

Training and Education CoreU54NS079202 · NINDS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI LEIN, PAMELA J · 2012 to 2021
$35.7M
Resource for the Development of Biomedical Accelerator Mass Spectrometry (AMS)P41GM103483 · NIGMS · UNIVERSITY OF CALIF-LAWRNC LVRMR NAT LAB · PI TURTELTAUB, KENNETH W. · 2012 to 2019
$12.0M
NIGMS NIH HHS 8P41GM103483NIGMS NIH HHS P41 GM103483NINDS NIH HHS U54 NS079202
6 · The paper itself

Abstract

Use of the highly toxic and easily prepared rodenticide tetramethylenedisulfotetramine (TETS) was banned after thousands of accidental or intentional human poisonings, but it is of continued concern as a chemical threat agent. TETS is a noncompetitive blocker of the GABA type A receptor (GABAAR), but its molecular interaction has not been directly established for lack of a suitable radioligand to localize the binding site. We synthesized [(14)C]TETS (14 mCi/mmol, radiochemical purity >99%) by reacting sulfamide with H(14)CHO and s-trioxane then completion of the sequential cyclization with excess HCHO. The outstanding radiocarbon sensitivity of accelerator mass spectrometry (AMS) allowed the use of [(14)C]TETS in neuroreceptor binding studies with rat brain membranes in comparison with the standard GABAAR radioligand 4'-ethynyl-4-n-[(3)H]propylbicycloorthobenzoate ([(3)H]EBOB) (46 Ci/mmol), illustrating the use of AMS for characterizing the binding sites of high-affinity (14)C radioligands. Fourteen noncompetitive antagonists of widely diverse chemotypes assayed at 1 or 10 µM inhibited [(14)C]TETS and [(3)H]EBOB binding to a similar extent (r(2) = 0.71). Molecular dynamics simulations of these 14 toxicants in the pore region of the α1β2γ2 GABAAR predict unique and significant polar interactions for TETS with α1T1' and γ2S2', which are not observed for EBOB or the GABAergic insecticides. Several GABAAR modulators similarly inhibited [(14)C]TETS and [(3)H]EBOB binding, including midazolam, flurazepam, avermectin Ba1, baclofen, isoguvacine, and propofol, at 1 or 10 μM, providing an in vitro system for recognizing candidate antidotes.

Indexed as

AmidesAnimalsBinding, CompetitiveBridged Bicyclo Compounds, HeterocyclicBridged-Ring CompoundsCarbon IsotopesCarbon RadioisotopesFormaldehydeGABA AgonistsGABA-A Receptor AntagonistsHeterocyclic CompoundsHumansHypnotics and SedativesInsecticidesIsonicotinic AcidsModels, Molecular1-(4-ethynylphenyl)-4-propyl-2,6,7-trioxabicyclo(2.2.2)octaneAmidesBridged Bicyclo Compounds, HeterocyclicBridged-Ring CompoundsCarbon IsotopesCarbon RadioisotopesFormaldehydeGABA AgonistsGABA-A Receptor AntagonistsHeterocyclic CompoundsHypnotics and SedativesInsecticidesisoguvacineIsonicotinic AcidsPropofolPyridoxineReceptors, GABA-As-trioxaneSulfurtetramethylenedisulfotetramineVitamin B Complexconvulsantmolecular modelingneurotoxicity

Identifiers

PMID24912155
PMCPMC4060666
OpenAlexW2075697977

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.