Evidence map›Paper›PMID 37790558›Full record

ArticleResearch square2023

Allosteric Site Mediates Inhibition of Tonic NMDA Receptor Activity by Low Dose Ketamine.

Gabriela Popescu, Jamie Abbott, Han Wen, Beiying Liu, Sheila Gupta, Gary Iacobucci, Wenjun Zheng

Open access · greenAbstract readPreprint
In one paragraph

Article in Research square, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed, 0 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Gabriela PopescuJacobs School of Medicine and Biomedical Sciences/University at Buffalo, SUNY.ORCID 0000-0003-4658-2002
Jamie AbbottJacobs School of Medicine and Biomedical Sciences/University at Buffalo, SUN.
Beiying LiuSUNY Buffalo.
Sheila GuptaJacobs School of Medicine and Biomedical Sciences/University at Buffalo, SUN.
Gary IacobucciUniversity at Buffalo.ORCID 0000-0001-7596-8380
Wenjun Zheng
Buffalo State University · US

Funding

Experience-Dependent Reorganization of Excitatory Synapse ConnectivityR01MH118298 · NIMH · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI PAN, JEN QIAN, POPESCU, GABRIELA K · 2019 to 2023
$3.3M
Molecular Physiology of NMDA ReceptorsR35NS132248 · NINDS · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI Gabriela K Popescu · 2023 to 2026
$2.3M
Gating Mechanism of NMDA ReceptorsR01NS108750 · NINDS · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI POPESCU, GABRIELA K · 2019 to 2023
$1.5M
NIMH NIH HHS R01 MH118298NINDS NIH HHS R01 NS108750NINDS NIH HHS R35 NS132248
6 · The paper itself

Abstract

Ketamine, a general anesthetic, has rapid and sustained antidepressant effects when administered at lower doses. At anesthetic doses, ketamine causes a drastic reduction in excitatory transmission by lodging in the centrally located hydrophilic pore of the NMDA receptor, where it blocks ionic flow. In contrast, the molecular and cellular targets responsible for the antidepressant effects of ketamine remain controversial. Here, we report functional and structural evidence that, at nanomolar concentrations, ketamine interacts with membrane-accessible hydrophobic sites where it stabilizes desensitized receptors to cause an incomplete, voltage- and pH-dependent reduction in NMDA receptor activity. This allosteric mechanism spares brief receptor activations and reduces preferentially currents from tonically active receptors. The hydrophobic site is a promising target for safe and effective therapies against acute and chronic neurodegeneration.

Identifiers

PMID37790558
PMCPMC10543308
OpenAlexW4386923581

What OpenQuestion holds

Textmetadata
LicenceCC BY
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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.