American Heart Journal
Volume 156, Issue 2, Supplement , Pages 10S-15S , August 2008

Pharmacology of emerging novel platelet inhibitors

  • Dominick J. Angiolillo, MD, PhD, FACC, FESC

      Affiliations

    • Corresponding Author InformationReprint requests: Dominick J. Angiolillo, MD, PhD, FACC, FESC, Division of Cardiology, University of Florida-Shands Jacksonville, 655 West 8th St, Jacksonville, FL 32209.
    • ,
  • Piera Capranzano, MD

References 

  1. Wallentin L, Varenhorst C, James S, et al. Prasugrel achieves greater and faster P2Y12 receptor-mediated platelet inhibition than clopidogrel due to more efficient generation of its active metabolite in aspirin-treated patients with coronary artery disease. Eur Heart J. 2008;29:21–30
  2. Payne CD, Li YG, Small DS, et al. Increased active metabolite formation explains the greater platelet inhibition with prasugrel compared to high-dose clopidogrel. J Cardiovasc Pharmacol. 2007;50:555–562
  3. Farid NA, Smith RL, Gillespie TA, et al. The disposition of prasugrel, a novel thienopyridine, in humans. Drug Metab Dispos. 2007;35:1096–1104
  4. Rehmel JL, Eckstein JA, Farid NA, et al. Interactions of two major metabolites of prasugrel, a thienopyridine antiplatelet agent with the cytochromes P450. Drug Metab Dispos. 2006;34:600–607
  5. Farid NA, Payne CD, Small DS, et al. Cytochrome P450 3A inhibition by ketoconazole affects prasugrel and clopidogrel pharmacokinetics and pharmacodynamics differently. Clin Pharmacol Ther. 2007;81:735–741
  6. Niitsu Y, Jakubowski JA, Sugidachi A, et al. Pharmacology of CS-747 (prasugrel, LY640315), a novel, potent antiplatelet agent with in vivo P2Y12 receptor antagonist activity. Semin Thromb Hemost. 2005;31:184–194
  7. Sugidachi A, Asai F, Ogawa T, et al. The in vivo pharmacological profile of CS-747, a novel antiplatelet agent with platelet ADP receptor antagonist properties. Br J Pharmacol. 2000;129:1439–1446
  8. van Giezen JJ, Humphries RG. Preclinical and clinical studies with selective reversible direct P2Y12 antagonists. Semin Thromb Hemost. 2005;31:195–204
  9. Tantry US, Bliden KP, Gurbel PA. AZD6140. Expert Opin Investig Drugs. 2007;16:225–229
  10. Nassim MA, Sanderson JB, Clarke C, et al. Investigation of the novel P2T receptor antagonist AR-C69931MX on ex vivo adenosine diphosphate-induced platelet aggregation and bleeding time in healthy volunteers. [abstract] J Am Coll Cardiol. 1999;33(2 Suppl A):255A
  11. Ingall AH, Dixon J, Bailey A, et al. Antagonists of the platelet P2T receptor: a novel approach to antithrombotic therapy. J Med Chem. 1999;42:213–220
  12. Huang J, Driscoll EM, Gonzales ML, et al. Prevention of arterial thrombosis by intravenously administered platelet P2T receptor antagonist AR-C69931MX in a canine model. J Pharmacol Exp Ther. 2000;295:492–499
  13. Humphries RG, Tomlinson W, Ingall AH, et al. Effect of the novel P2T receptor antagonist, AR-C69931MX, on thrombosis and hemostasis in the dog: comparison with GPIIb/IIIa antagonists. [abstract] Haematologica. 2000;85(Suppl):91–92
  14. van Gestel MA, Heemskerk JW, Slaaf DW, et al. In vivo blockade of platelet ADP receptor P2Y12 reduces embolus and thrombus formation but not thrombus stability. Arterioscler Thromb Vasc Biol. 2003;23:518–523
  15. Wang K, Zhou X, Zhou Z, et al. Blockade of the platelet P2Y12 receptor by AR-C69931MX sustains coronary artery recanalization and improves the myocardial tissue perfusion in a canine thrombosis model. Arterioscler Thromb Vasc Biol. 2003;23:357–362
  16. Vu TKH, Hung DT, Wheaton VI, et al. Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation. Cell. 1991;64:1057–1068
  17. Zhang W, Colman RW. Thrombin regulates intracellular cyclic AMP concentration in human platelets through phosphorylation/activation of phosphodiesterase 3A. Blood. 2007;110:1475–1482
  18. Derian CK, Maryanoff BE, Zhang HC, et al. Therapeutic potential of protease-activated receptor-1 antagonists. Expert Opin Investig Drugs. 2003;12:209–221
  19. Coughlin SR, Camerer E. PARticipation in inflammation. J Clin Invest. 2003;111:25–27
  20. Kosoglou T, Larisa Reyderman L, Robert R, et al. Pharmacodynamics and pharmacokinetics of a novel protease-activated receptor (PAR-1) antagonist SCH 530348. [abstract] Circulation. 2005;112(Suppl):II-32
  21. Gretler DD, Conley PB, Andre P, et al. “First in human” experience with PRT060128, a new direct-acting, reversible, P2Y12 inhibitor for IV and oral use. [abstract] J Am Coll Cardiol. 2007;49(Suppl):326A
  22. Lieu HD, Conley PB, Andre P, et al. Initial intravenous experience with PRT060128 (PRT128), an orally-available, direct-acting, and reversible P2Y12 inhibitor. J Thromb Haemost. 2007;5(Suppl 2):P-T-292;[abstract]
  23. Kogushi M, Yokohama H, Kitamura S, et al. Effects of E5555, a protease-activated receptor-1 antagonist, on the inflammatory markers in vitro. [abstract] J Thromb Haemost. 2007;5(Suppl 1):P-M-059

 Conflicts of Interest: Dominick J. Angiolillo, MD, PhD, FACC, FESC has declared the following conflicts of interest: Honoraria/Lectures: Bristol Myers Squibb (New York, NY); Sanofi-Aventis (Bridgewater, NJ); Eli Lilly and Company (Indianapolis, IN); Daiichi Sankyo, Inc (Parsippany, NJ). Honoraria/Advisory board: Bristol Myers Squibb; Sanofi-Aventis; Eli Lilly Co; Daiichi Sankyo, Inc.; The Medicines Company (Parsippany, NJ); Portola (San Francisco, CA); Novartis (East Hanover, NJ). Research Grants: GlaxoSmithKline (Brentford, London, United Kingdom); Otsuka (Tokyo, Japan). Piera Capranzano, MD, has declared no conflicts of interest.

PII: S0002-8703(08)00471-7

doi: 10.1016/j.ahj.2008.06.004

American Heart Journal
Volume 156, Issue 2, Supplement , Pages 10S-15S , August 2008

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