Evidence map›Paper›PMID 24102184›Full record

ArticleBritish journal of pharmacology2014

Characterization of a novel multifunctional resveratrol derivative for the treatment of atrial fibrillation.

Istvan Baczko, David Liknes, Wei Yang, Kevin C Hamming, Gavin Searle, Kristian Jaeger, Zoltan Husti, Viktor Juhasz, Gergely Klausz, Robert Pap and 8 more

Open access · bronzeAbstract read
In one paragraph

Article in British journal of pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.0field-weighted citation impact, top 13% 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

17 citing papers in PubMed, 40 citations in OpenAlex.

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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

18 authors at 3 institutions in 2 countries.

Istvan BaczkoDepartment of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary.
David Liknes
Wei Yang
Kevin C Hamming
Gavin Searle
Kristian Jaeger
Zoltan Husti
Viktor Juhasz
Gergely Klausz
Robert Pap
Laszlo Saghy
Andras Varro
Vernon Dolinsky
Shaohua Wang
Vivek Rauniyar
Dennis Hall
Jason Rb Dyck
Peter E Light
University of Alberta · CAUniversity of Szeged · HUUniversity of Manitoba · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

background and purposeAtrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with an increased risk for stroke, heart failure and cardiovascular-related mortality. Candidate targets for anti-AF drugs include a potassium channel K(v)1.5, and the ionic currents I(KACh) and late I(Na), along with increased oxidative stress and activation of NFAT-mediated gene transcription. As pharmacological management of AF is currently suboptimal, we have designed and characterized a multifunctional small molecule, compound 1 (C1), to target these ion channels and pathways. EXPERIMENTAL APPROACH: We made whole-cell patch-clamp recordings of recombinant ion channels, human atrial I(Kur), rat atrial I(KACh), cellular recordings of contractility and calcium transient measurements in tsA201 cells, human atrial samples and rat myocytes. We also used a model of inducible AF in dogs. KEY

resultsC1 inhibited human peak and late K(v)1.5 currents, frequency-dependently, with IC₅₀ of 0.36 and 0.11 μmol·L(-1) respectively. C1 inhibited I(KACh)(IC₅₀ of 1.9 μmol·L(-1)) and the Na(v)1.5 sodium channel current (IC₅₀s of 3 and 1 μmol·L(-1) for peak and late components respectively). C1 (1 μmol·L(-1)) significantly delayed contractile and calcium dysfunction in rat ventricular myocytes treated with 3 nmol·L(-1) sea anemone toxin (ATX-II). C1 weakly inhibited the hERG channel and maintained antioxidant and NFAT-inhibitory properties comparable to the parent molecule, resveratrol. In a model of inducible AF in conscious dogs, C1 (1 mg·kg(-1)) reduced the average and total AF duration. CONCLUSION AND IMPLICATIONS: C1 behaved as a promising multifunctional small molecule targeting a number of key pathways involved in AF.

Indexed as

Action PotentialsAdultAgedAnimalsAnimals, NewbornAnti-Arrhythmia AgentsAntioxidantsAtrial FibrillationDisease Models, AnimalDogsDose-Response Relationship, DrugERG1 Potassium ChannelEther-A-Go-Go Potassium ChannelsExcitation Contraction CouplingG Protein-Coupled Inwardly-Rectifying Potassium ChannelsHEK293 CellsAnti-Arrhythmia AgentsAntioxidantsERG1 Potassium ChannelEther-A-Go-Go Potassium ChannelsG Protein-Coupled Inwardly-Rectifying Potassium ChannelsKCNA5 protein, humanKCNH2 protein, humanKv1.5 Potassium ChannelNAV1.5 Voltage-Gated Sodium ChannelNFATC Transcription FactorsPotassium Channel BlockersResveratrolSCN5A protein, humanSodium Channel BlockersStilbenesatrial fibrillationelectrophysiologyion channelsKv1.5pharmacologyresveratrol

Identifiers

PMID24102184
PMCPMC3874699
OpenAlexW1485003660

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.