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Pleiotropic effects of clopidogrel

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Abstract

Clopidogrel is a widely prescribed prodrug with anti-thrombotic activity through irreversible inhibition of the P2Y12 receptor on platelets. It is FDA-approved for the clinical management of thrombotic diseases like unstable angina, myocardial infarction, stroke, and during percutaneous coronary interventions. Hepatic clopidogrel metabolism generates several distinct metabolites. Only one of these metabolites is responsible for inhibiting the platelet P2Y12 receptor. Importantly, various non-hemostatic effects of clopidogrel therapy have been described. These non-hemostatic effects are perhaps unsurprising, as P2Y12 receptor expression has been reported in multiple tissues, including osteoblasts, leukocytes, as well as vascular endothelium and smooth muscle. While the “inactive” metabolites have been commonly thought to be biologically inert, recent findings have uncovered P2Y12 receptor-independent effects of clopidogrel treatment that may be mediated by understudied metabolites. In this review, we summarize both the P2Y12 receptor-mediated and non-P2Y12 receptor-mediated effects of clopidogrel and its metabolites in various tissues.

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Fig. 1
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Fig. 3

Modified from Kuszynski et al. [95]

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Data availability

All the data analyzed in this review are available in the cited references.

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Acknowledgements

The authors wish to thank Dr. James Luyendyk, Michigan State University, for proofreading and helpful suggestions.

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  1. Department of Pharmacology and Toxicology, College of Veterinary Medicine, Michigan State University, 1355 Bogue Street, B336 Life Science, East Lansing, MI, USA

    Dawn S. Kuszynski & D. Adam Lauver

  2. Institute of Integrative Toxicology, Michigan State University, East Lansing, MI, USA

    Dawn S. Kuszynski

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Kuszynski, D.S., Lauver, D.A. Pleiotropic effects of clopidogrel. Purinergic Signalling 18, 253–265 (2022). https://doi.org/10.1007/s11302-022-09876-0

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