Co-administration of nitric oxide-aspirin (NCX-4016) and aspirin prevents platelet and monocyte activation and protects against gastric damage induced by aspirin in humans

Journal of the American College of Cardiology
Stefano FiorucciPietro Minuz

Abstract

The goal of this study was to test the hypothesis that NCX-4016 may have broader anti-inflammatory and antithrombotic effects as well as better gastric tolerability than aspirin in humans. NCX-4016 is an aspirin derivative containing a nitric oxide-releasing moiety that prevents platelet activation and modulates tissue factor (TF) expression and cytokine release from lipopolysaccharide (LPS)-stimulated monocytes. This was a blind-observer, placebo-controlled, parallel-group study in which 48 healthy subjects were randomized to receive NCX-4016 800 mg twice a day, NCX-4016 800 mg twice a day plus aspirin 325 mg, aspirin 325 mg, or placebo for 21 days. Similar to aspirin alone, NCX-4016 effectively inhibited platelet aggregation induced by 0.6 mmol/ arachidonic acid, clot-stimulated thromboxane (TX) B2 generation in whole blood, and urinary excretion of 11-dehydro-TXB2. Unlike aspirin alone, the administration of NCX-4016 significantly inhibited TF expression in monocytes stimulated ex vivo with 10 micromol/l LPS (determined by flow-cytometry analysis of TF on CD14 positive cells). NCX-4016 also inhibited the rapid TF expression induced in monocytes by a proteinase activated receptor agonist (thrombin receptor activator protein, ...Continue Reading

References

Oct 17, 1991·The New England Journal of Medicine·R J ClarkeG A FitzGerald
Nov 14, 1997·The Journal of Biological Chemistry·A D SchecterM B Taubman
Jan 14, 1999·The New England Journal of Medicine·R Ross
Jun 22, 1999·The New England Journal of Medicine·G D Sloop
Jun 14, 2000·European Journal of Pharmacology·S MomiP Gresele
Oct 14, 2000·Arteriosclerosis, Thrombosis, and Vascular Biology·E LindmarkA Siegbahn
Jul 5, 2001·Proceedings of the National Academy of Sciences of the United States of America·M Riewald, W Ruf
Oct 19, 2001·British Journal of Pharmacology·P MinuzA Lechi
Dec 26, 2001·The New England Journal of Medicine·F Catella-LawsonG A FitzGerald
Jul 18, 2002·Nature Reviews. Drug Discovery·John L WallaceStefano Fiorucci
Dec 20, 2002·Nature·Peter Libby
Sep 10, 2003·Proceedings of the National Academy of Sciences of the United States of America·Stefano FiorucciAntonio Morelli

❮ Previous
Next ❯

Citations

Jul 10, 2009·Current Opinion in Hematology·Galia Spectre, David Varon
Nov 26, 2008·Arthritis Research & Therapy·Angel Lanas
May 23, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Marcin MagierowskiTomasz Brzozowski
Dec 16, 2006·Endothelium : Journal of Endothelial Cell Research·Dimitris TousoulisChristodoulos Stefanadis
Jul 19, 2005·Expert Opinion on Investigational Drugs·Roberto ScatenaBruno Giardina
Nov 1, 2005·Expert Opinion on Investigational Drugs·Brendan J R Whittle
Dec 17, 2011·International Immunopharmacology·Muzammal HussainMuti Ur Rehman
May 17, 2006·British Journal of Pharmacology·Catriona M TurnbullIan L Megson
Oct 10, 2006·International Journal of Cardiology·Roberto LorussoAndrea Giustina
Sep 26, 2006·International Journal of Cardiology·Charalambos AntoniadesChristodoulos Stefanadis
Nov 16, 2006·Expert Opinion on Therapeutic Targets·Catriona M TurnbullIan L Megson
Feb 25, 2015·Journal of Gastroenterology·Eleonora DistruttiStefano Fiorucci
Sep 11, 2004·Journal of the American College of Cardiology·Richard I Levin
Dec 23, 2016·Medicinal Research Reviews·Catarina Pereira-LeiteSalette Reis
Jan 5, 2005·Journal of the American College of Cardiology·Anthony N DemariaSotirios Tsimikas
Apr 3, 2007·British Journal of Pharmacology·M R Miller, I L Megson
Jan 8, 2021·Cancer Metastasis Reviews·Kathryn ColeJames E Talmadge
Jul 3, 2021·International Journal of Molecular Sciences·Alicja NowaczykGrzegorz Grześk

❮ Previous
Next ❯

Related Concepts

Related Feeds

Blood Clotting Disorders

Thrombophilia includes conditions with increased tendency for excessive blood clotting. Blood clotting occurs when the body has insufficient amounts of specialized proteins that make blood clot and stop bleeding. Here is the latest research on blood clotting disorders.

Cardiology Journals

Discover the latest cardiology research in this collection of the top cardiology journals.