Evidence map›Paper›PMID 42481720›Full record

ArticleNature structural & molecular biology2026

Structural and functional basis of antinociceptive action of χ-conotoxin AoIA at the noradrenaline transporter.

Oliver J V Belleza, Heng Zhang, Helmut Schmidhammer, Tye I Gonzalez, Cosmin I Ciotu, Nataša Tomašević, Carlo Martin M Ocampo, Jomari C Fernando, Johannes Koehbach, Paula Schwarz and 17 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature structural & molecular biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

27 authors.

Oliver J V Belleza *Institute of Pharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.ORCID http://orcid.org/0000-0002-6383-6636
Heng Zhang *State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Helmut SchmidhammerDepartment of Pharmaceutical Chemistry, Institute of Pharmacy and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innsbruck, Austria.
Tye I GonzalezSchool of Biomedical Sciences, The University of Queensland, Brisbane, Queensland, Australia.ORCID http://orcid.org/0000-0003-4756-1182
Cosmin I CiotuInstitute of Physiology, Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
Nataša TomaševićInstitute of Pharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
Carlo Martin M OcampoInstitute of Chemistry, University of the Philippines - Diliman, Quezon City, Philippines.ORCID http://orcid.org/0000-0002-9162-1958
Jomari C FernandoInstitute of Chemistry, University of the Philippines - Diliman, Quezon City, Philippines.
Johannes KoehbachSchool of Biomedical Sciences, The University of Queensland, Brisbane, Queensland, Australia.
Paula SchwarzInstitute of Pharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
Mounaf Al MakhloufInstitute of Pharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.ORCID http://orcid.org/0009-0003-2971-8390
Gabor TajtiInstitute of Physiology, Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
Simon HasingerInstitute of Pharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
Nina KastnerInstitute of Pharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
Orcun AvsarInstitute of Pharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
Bernhard RetzlInstitute of Pharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
Kathrin JäntschInstitute of Pharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
Yi JiangLingang Laboratory, Shanghai, China.ORCID http://orcid.org/0000-0002-0723-1413
Roland HellingerInstitute of Pharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
Michael J M FischerInstitute of Physiology, Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.ORCID http://orcid.org/0000-0002-3811-7066
K Johan RosengrenSchool of Biomedical Sciences, The University of Queensland, Brisbane, Queensland, Australia.ORCID http://orcid.org/0000-0002-5007-8434
Christian W GruberInstitute of Pharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.ORCID http://orcid.org/0000-0001-6060-7048
Aaron Joseph L VillarazaInstitute of Chemistry, University of the Philippines - Diliman, Quezon City, Philippines.ORCID http://orcid.org/0000-0003-0514-3329
Thomas StocknerInstitute of Pharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.ORCID http://orcid.org/0000-0002-7071-8283
Mariana SpeteaDepartment of Pharmaceutical Chemistry, Institute of Pharmacy and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innsbruck, Austria.ORCID http://orcid.org/0000-0002-2379-5358
H Eric XuState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China. eric.xu@simm.ac.cn.ORCID http://orcid.org/0000-0002-6829-8144
Harald H SitteInstitute of Pharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria. harald.sitte@meduniwien.ac.at.ORCID http://orcid.org/0000-0002-1339-7444

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The χ-conotoxins are venom-derived peptides that specifically target the noradrenaline transporter (also known as norepinephrine transporter, NET). Regulation of noradrenergic signaling by NET affects neurophysiological processes, including pain. Therefore, the χ-conotoxin MrIA and its synthetic analogs have been previously investigated for their analgesic activity. Here we describe the synthesis and pharmacological characterization of χ-AoIA, a peptide that selectively inhibits NET with a higher potency compared to MrIA in in vitro radiotracer flux assays. Furthermore, we resolved the structure of the human NET:χ-AoIA complex by cryogenic electron microscopy, which revealed an atypical binding mode consisting of both the central binding site and the outer vestibule of the transporter. Lastly, χ-AoIA displays antinociceptive efficacy in a model of inflammatory pain after subcutaneous administration in mice. Our results demonstrate the efficacy of χ-AoIA as a highly selective ligand of NET and provide a mechanistic basis for its potential development as a nonopioid analgesic.

Indexed as

AnalgesicsConotoxinsNorepinephrine Plasma Membrane Transport ProteinsAnimalsBinding SitesCryoelectron MicroscopyHumansMaleMiceModels, MolecularPainAnalgesicsConotoxinsNorepinephrine Plasma Membrane Transport Proteins

Identifiers

PMID42481720
PMCPMC13561870

What Socratic 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 Socratic graph.