Evidence map›Paper›PMID 21913899›Full record

ArticleBritish journal of pharmacology2012

Antiplatelet and antithrombotic effect of F 16618, a new thrombin proteinase-activated receptor-1 (PAR1) antagonist.

M Dumas, F Nadal-Wollbold, P Gaussem, M Perez, T Mirault, R Létienne, T Bourbon, F Grelac, B Le Grand, C Bachelot-Loza

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in British journal of pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Article
  5. Novel Antiplatelet Therapies for Atherothrombotic Diseases.Arteriosclerosis, thrombosis, and vascular biology · 2019
    Review
  6. Article
  7. Targeting PAR1: Now What?Trends in pharmacological sciences · 2017
    Review
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

10 authors.

M DumasInserm UMR S 765, Faculté de Pharmacie, Paris, FranceUniversité Paris Descartes, Sorbonne Paris Cité, Paris, FranceCentre de Recherche Pierre Fabre, 17, Avenue Jean Moulin, Castres cedex, FranceAP-HP, Hôpital Européen Georges Pompidou, Service d'Hématologie Biologique, Paris, France.
F Nadal-WollboldInserm UMR S 765, Faculté de Pharmacie, Paris, FranceUniversité Paris Descartes, Sorbonne Paris Cité, Paris, FranceCentre de Recherche Pierre Fabre, 17, Avenue Jean Moulin, Castres cedex, FranceAP-HP, Hôpital Européen Georges Pompidou, Service d'Hématologie Biologique, Paris, France.
P GaussemInserm UMR S 765, Faculté de Pharmacie, Paris, FranceUniversité Paris Descartes, Sorbonne Paris Cité, Paris, FranceCentre de Recherche Pierre Fabre, 17, Avenue Jean Moulin, Castres cedex, FranceAP-HP, Hôpital Européen Georges Pompidou, Service d'Hématologie Biologique, Paris, France.
M PerezInserm UMR S 765, Faculté de Pharmacie, Paris, FranceUniversité Paris Descartes, Sorbonne Paris Cité, Paris, FranceCentre de Recherche Pierre Fabre, 17, Avenue Jean Moulin, Castres cedex, FranceAP-HP, Hôpital Européen Georges Pompidou, Service d'Hématologie Biologique, Paris, France.
T MiraultInserm UMR S 765, Faculté de Pharmacie, Paris, FranceUniversité Paris Descartes, Sorbonne Paris Cité, Paris, FranceCentre de Recherche Pierre Fabre, 17, Avenue Jean Moulin, Castres cedex, FranceAP-HP, Hôpital Européen Georges Pompidou, Service d'Hématologie Biologique, Paris, France.
R LétienneInserm UMR S 765, Faculté de Pharmacie, Paris, FranceUniversité Paris Descartes, Sorbonne Paris Cité, Paris, FranceCentre de Recherche Pierre Fabre, 17, Avenue Jean Moulin, Castres cedex, FranceAP-HP, Hôpital Européen Georges Pompidou, Service d'Hématologie Biologique, Paris, France.
T BourbonInserm UMR S 765, Faculté de Pharmacie, Paris, FranceUniversité Paris Descartes, Sorbonne Paris Cité, Paris, FranceCentre de Recherche Pierre Fabre, 17, Avenue Jean Moulin, Castres cedex, FranceAP-HP, Hôpital Européen Georges Pompidou, Service d'Hématologie Biologique, Paris, France.
F GrelacInserm UMR S 765, Faculté de Pharmacie, Paris, FranceUniversité Paris Descartes, Sorbonne Paris Cité, Paris, FranceCentre de Recherche Pierre Fabre, 17, Avenue Jean Moulin, Castres cedex, FranceAP-HP, Hôpital Européen Georges Pompidou, Service d'Hématologie Biologique, Paris, France.
B Le GrandInserm UMR S 765, Faculté de Pharmacie, Paris, FranceUniversité Paris Descartes, Sorbonne Paris Cité, Paris, FranceCentre de Recherche Pierre Fabre, 17, Avenue Jean Moulin, Castres cedex, FranceAP-HP, Hôpital Européen Georges Pompidou, Service d'Hématologie Biologique, Paris, France.
C Bachelot-LozaInserm UMR S 765, Faculté de Pharmacie, Paris, FranceUniversité Paris Descartes, Sorbonne Paris Cité, Paris, FranceCentre de Recherche Pierre Fabre, 17, Avenue Jean Moulin, Castres cedex, FranceAP-HP, Hôpital Européen Georges Pompidou, Service d'Hématologie Biologique, Paris, France.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

background and purposeNew antithrombotic agents with the potential to prevent atherothrombotic complications are being developed to target receptors on platelets and other cells involved in plaque growth. The aim of this study was to investigate the antiplatelet effects of F 16618, a new non-peptidic PAR1 (thrombin receptor) antagonist. EXPERIMENTAL APPROACH: We investigated the inhibitory effect of F 16618 on human platelet aggregation ex vivo, in whole blood and washed platelets, by using a multiple-electrode platelet aggregometer based on impedance and an optical aggregometer, respectively. Its effects on whole-blood haemostasis (clot parameters) were analysed with the ROTEM thromboelastometry device and the platelet function analyser PFA-100. A guinea-pig model of arterial thrombosis was used to investigate its effects on thrombus formation in vivo. KEY

resultsF 16618 inhibited PAR1 agonist peptide (SFLLR-peptide)-induced washed platelet aggregation ex vivo. This effect was concentration-dependent and exhibited a competitive inhibition profile. Washed platelet aggregation, as well as P-selectin expression induced by thrombin, were significantly inhibited by 10 µM F 16618. In whole-blood experiments, 20 µM F 16618 inhibited SFLLR-induced platelet aggregation by 49%. In contrast, it had no effect on whole-blood haemostasis. In the guinea-pig model of carotid thrombosis, 0.32 mg·kg(-1) F 16618 doubled the occlusion time. CONCLUSIONS AND IMPLICATIONS: F 16618 was shown to have strong antithrombotic activity in vivo and moderate antiplatelet effects ex vivo. As these effects were not associated with major effects on physiological haemostasis, this molecule is a good antiplatelet drug candidate for use either alone or in combination with current treatments.

Indexed as

Platelet Aggregation InhibitorsAnimalsCarotid Artery ThrombosisCollagenFibrinolytic AgentsGuinea PigsHemostasisHumansMaleOligopeptidesPiperazinesPlatelet AggregationPyridinesReceptor, PAR-1Thrombin2-(5-oxo-5-(4-pyridin-2-ylpiperazin-1-yl)penta-1,3-dienyl)benzonitrileC186 65CollagenFibrinolytic AgentsOligopeptidesPiperazinesPlatelet Aggregation InhibitorsPyridinesReceptor, PAR-1Thrombin

Identifiers

PMID21913899
PMCPMC3372833

What OpenQuestion holds

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Registered trials

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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.