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Dipyridamole and PDE Inhibitors

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Platelets in Thrombotic and Non-Thrombotic Disorders

Abstract

Inhibition of platelet aggregation can be achieved either by the blockade of membrane receptors or by interaction with intracellular signaling pathways. Cyclic adenosine 3′,5′-monophosphate (cAMP) and cyclic guanosine 3′,5-monophosphate (cGMP) are two critical intracellular second messengers provided with strong inhibitory activity on fundamental platelet function. Phosphodiesterases (PDEs), by catalyzing the hydrolysis of cAMP and cGMP, limit the intracellular levels of cyclic nucleotides thus regulating platelet function. The inhibition of PDEs may therefore exert a strong platelet inhibitory effect. In mammalian tissues, 11 structurally related but functionally distinct PDE gene families (PDE1–PDE11) have been described. Platelets possess three PDE isoforms, PDE2, PDE3, and PDE5, with different selectivity for cAMP and cGMP. Several nonselective or isoenzyme-selective PDE inhibitors have been developed, and some of them have entered clinical use as antiplatelet agents. This review will focus on the effect of PDE2, PDE3, and PDE5 inhibitors on platelet function and on the evidence for an antithrombotic action of some of them and in particular of dipyridamole and cilostazol.

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Authors and Affiliations

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

    Paolo Gresele MD, PhD, Stefania Momi & Emanuela Falcinelli

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  1. Paolo Gresele MD, PhD
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  2. Stefania Momi
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  3. Emanuela Falcinelli
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Correspondence to Paolo Gresele MD, PhD .

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Editors and Affiliations

  1. Department of Medicine, Section of Internal and Cardiovascular Medicine, University of Perugia , Perugia, Italy

    Paolo Gresele

  2. Houston Methodist Hospital , Houston, Texas, USA

    Neal S. Kleiman

  3. Bloodworks Northwest, University of Washington , Seattle, Washington, USA

    José A. Lopez

  4. Sackler Inst of Pulmonary Pharmacol, King’s College London, London, United Kingdom

    Clive P. Page

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Gresele, P., Momi, S., Falcinelli, E. (2017). Dipyridamole and PDE Inhibitors. In: Gresele, P., Kleiman, N., Lopez, J., Page, C. (eds) Platelets in Thrombotic and Non-Thrombotic Disorders. Springer, Cham. https://doi.org/10.1007/978-3-319-47462-5_86

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