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Intracellular Signaling as a Potential Target for Antiplatelet Therapy

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Antiplatelet Agents

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 210))

Abstract

Three classes of inhibitors of platelet aggregation have demonstrated substantial clinical benfits. Aspirin acts by irreversibly inhibiting COX-1 and therefore blocking the synthesis of proaggregatory thromboxane A 2 (TxA2). The indirect acting (ticlopidine, clopidogrel, prasugrel) and the direct acting (ticagrelor) antagonists of P2Y12 block the thrombus stabilizing activity of ADP. Parenteral GP IIb-IIIa inhibitors directly block platelet-platelet interactions. Despite well-established benefits, all antiplatelet agents have important limitations: increased bleeding and gastrointestinal toxicities (aspirin), high incidence of thrombotic thrombocytopenic purpura (ticlopidine), potentially nonresponders (clopidogrel), severe bleeding (prasugrel, GP IIb-IIIa antagonists) and “complicated” relationships with aspirin ticagrelor). In this chapter, we present the genetic and pharmacological evidence that supports the development and expectations associated with novel antiplatelet strategies directed at intrasignaling pathways.

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Authors and Affiliations

  1. Portola Pharmaceuticals Inc, 270 E. Grand Avenue, Suite 22 South, San Francisco, CA, 94080, USA

    Patrick Andre

  2. Merck Research Laboratories, 126 E. Lincoln Avenue, Rahway, NJ, 07065, USA

    Patrick Andre

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  1. Patrick Andre
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Correspondence to Patrick Andre .

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Editors and Affiliations

  1. , Department of Internal Medicine, University of Perugia, Via E. dal Pozzo, Perugia, 06126, Italy

    Paolo Gresele

  2. Institute, The William Harvey Research, Charterhouse Square, London, EC1M6BQ, United Kingdom

    Gustav V. R Born

  3. Istituto di Farmacologia, Università Cattolica del S. Cuore, Largo F. Vito 1, Roma, 00168, Italy

    Carlo Patrono

  4. King's College London, Sackler Inst. Pulmonary Pharmacology, Waterloo Campus, London, SE1 9NH, United Kingdom

    Clive P. Page

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Andre, P. (2012). Intracellular Signaling as a Potential Target for Antiplatelet Therapy. In: Gresele, P., Born, G., Patrono, C., Page, C. (eds) Antiplatelet Agents. Handbook of Experimental Pharmacology, vol 210. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-29423-5_14

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