Evidence map›Paper›PMID 37194503›Full record

ArticleBritish journal of pharmacology2023

Pregnenolone sulfate analogues differentially modulate GABA

Martin Mortensen, Yue Xu, Mohamed A Shehata, Jacob Krall, Margot Ernst, Bente Frølund, Trevor G Smart

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in British journal of pharmacology, 2023. 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
0.9field-weighted citation impact, top 30% 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

1 citing paper in PubMed, 6 citations in OpenAlex.

  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

7 authors at 3 institutions in 3 countries.

Martin MortensenDepartment of Neuroscience, Physiology and Pharmacology, University College London, London, UK.
Yue XuDepartment of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Mohamed A ShehataDepartment of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Jacob KrallDepartment of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Margot ErnstDepartment of Pathology of the Nervous System, Center for Brain Research, Medical University of Vienna, Vienna, Austria.
Bente FrølundDepartment of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Trevor G SmartDepartment of Neuroscience, Physiology and Pharmacology, University College London, London, UK.
University of Copenhagen · DKUniversity College London · GBMedical University of Vienna · AT

Funding

Medical Research Council MR/T002581/1Wellcome TrustWellcome Trust 217199/Z/19/Z
6 · The paper itself

Abstract

background and purposeGABA EXPERIMENTAL APPROACH: New pregnenolone sulfate analogues were synthesised incorporating various heterocyclic substitutions located at the C-21 position on ring D. The pharmacological profiles of these compounds were assessed using electrophysiology and recombinant GABA KEY

resultsAll seven analogues retained a negative allosteric modulatory capability whilst exhibiting diverse potencies. Interestingly, we observed differential effects on GABA current decay by compounds incorporating either a six- (compound 5) or five-membered heterocyclic ring (compound 6) on C-21, which was independent of their potencies as inhibitors. We propose that differences in molecular charges, and the targeted binding of analogues to specific states of the GABA CONCLUSIONS AND IMPLICATIONS: Our findings reveal that heterocyclic addition to inhibitory neurosteroids not only affected their potency and macroscopic efficacy but also affected innate receptor mechanisms that underlie desensitisation. Acute modulation of macroscopic desensitisation will determine the degree and duration of GABA inhibition, which are vital for the integration of neural circuit activity. Discovery of this form of modulation could present an opportunity for next-generation GABA

Indexed as

PregnenoloneReceptors, GABA-Agamma-Aminobutyric AcidImidazolesSulfonamidesThiophenescompound 21gamma-Aminobutyric AcidImidazolesPregnenolonepregnenolone sulfateReceptors, GABA-ASulfonamidesThiopheneschemical analogueselectrophysiologyGABAGABAA receptorhuman embryonic kidney cellskinetic modellingmolecular dynamics simulationsorganic chemistrypregnenolone sulfaterecombinant expressionsynthesis

Identifiers

PMID37194503
PMCPMC10952582
OpenAlexW4376871262

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.