ArticleBritish journal of pharmacology2004
Synergistic action between inhibition of P2Y12/P2Y1 and P2Y12/thrombin in ADP- and thrombin-induced human platelet activation.
Article in British journal of pharmacology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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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.
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.
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Who cites it
29 citing papers in PubMed, 58 citations in OpenAlex.
- Pharmacodynamic Effects of Vorapaxar in Prior Myocardial Infarction Patients Treated With Potent Oral P2YJournal of the American Heart Association · 2020Trial
- Drug-like Antagonists of P2Y Receptor Subtypes: An Update.Journal of medicinal chemistry · 2025Review
- Progress Analysis of Personalized Antiplatelet Therapy in Patients with Coronary Heart Disease Undergoing Interventional Therapy.Reviews in cardiovascular medicine · 2024Review
- Platelets in Thrombosis and Atherosclerosis: A Double-Edged Sword.The American journal of pathology · 2024Review
- New insights into geraniol's antihemolytic, anti-inflammatory, antioxidant, and anticoagulant potentials using a combined biological and in silico screening strategy.Inflammopharmacology · 2022Article
- A novel definition and treatment of hyperinflammation in COVID-19 based on purinergic signalling.Purinergic signalling · 2022Review
- Article
- Influence ofJournal of the American Heart Association · 2021Article
- Inflammation and thrombosis in COVID-19 pathophysiology: proteinase-activated and purinergic receptors as drivers and candidate therapeutic targets.Physiological reviews · 2021Review
- ADP-Mediated Upregulation of Expression of CD62P on Human Platelets Is Critically Dependent on Co-Activation of P2Y1 and P2Y12 Receptors.Pharmaceuticals (Basel, Switzerland) · 2020Article
- Pharmacodynamic Effects of Vorapaxar in Patients With and Without Diabetes Mellitus: Results of the OPTIMUS-5 Study.JACC. Basic to translational science · 2019Article
- Creatine kinase, energy reserve, and hypertension: from bench to bedside.Annals of translational medicine · 2018Review
- Salvianolic acids from antithrombotic Traditional Chinese Medicine Danshen are antagonists of human P2YScientific reports · 2018Article
- Purinergic signalling links mechanical breath profile and alveolar mechanics with the pro-inflammatory innate immune response causing ventilation-induced lung injury.Purinergic signalling · 2017Review
- New highly active antiplatelet agents with dual specificity for platelet P2Y1 and P2Y12 adenosine diphosphate receptors.European journal of medicinal chemistry · 2016Article
- Blood cells: an historical account of the roles of purinergic signalling.Purinergic signalling · 2015Review
- Living in shear: platelets protect cancer cells from shear induced damage.Clinical & experimental metastasis · 2014Article
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- Article
- Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The objective of this study was to investigate if there is a synergistic effect of a combination of P2Y(12) and P2Y(1) inhibition and P2Y(12) and thrombin inhibition, on ADP- and thrombin-induced platelet activation, respectively. The rationale being that these combinations will cause a concurrent inhibition of both G alpha(q) and Galpha (i) signalling. Blood from healthy volunteers was preincubated with AR-C69931MX, a reversible P2Y(12) antagonist; MRS2179, a reversible P2Y(1) antagonist; or melagatran, a direct reversible thrombin inhibitor; alone or in various combinations prior to activation with ADP or thrombin. Platelet function in whole blood was assessed by flow cytometry using the antibody PAC-1 to estimate the expression of active alpha (IIb)beta(3) (the fibrinogen receptor GPIIb/IIIa). A synergistic effect was evaluated by comparing the concentrations in the different combinations with those of corresponding equipotent concentrations of each single inhibitor alone. The equipotent single concentrations were experimentally obtained from concentration response curves performed in parallel. A synergistic effect regarding inhibition of ADP-induced platelet activation (10 microM) was obtained with different combinations of AR-C69931MX and MRS2179. Inhibition of thrombin-induced platelet activation (2 nM) with combinations of AR-C69931MX and the thrombin inhibitor melagatran did also result in a strong synergistic effect. To our knowledge, this is the first time that data supporting a synergistic effect has been published for the inhibitor combinations described. Whether this synergistic effect in vitro also results in an improved antithrombotic effect in vivo with or without an increased risk of bleeding remains to be studied in well-conducted clinical studies.
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Registered trials
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.