Department of Pharmacology and Toxicology, College of Veterinary Medicine, Michigan State University, 1355 Bogue Street, B336 Life Science, East Lansing, MI, USA.
Institute of Integrative Toxicology, Michigan State University, East Lansing, MI, USA.
Purinergic Signal. 2022 Sep;18(3):253-265. doi: 10.1007/s11302-022-09876-0. Epub 2022 Jun 9.
Clopidogrel is a widely prescribed prodrug with anti-thrombotic activity through irreversible inhibition of the P2Y 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 P2Y receptor. Importantly, various non-hemostatic effects of clopidogrel therapy have been described. These non-hemostatic effects are perhaps unsurprising, as P2Y 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 P2Y receptor-independent effects of clopidogrel treatment that may be mediated by understudied metabolites. In this review, we summarize both the P2Y receptor-mediated and non-P2Y receptor-mediated effects of clopidogrel and its metabolites in various tissues.
氯吡格雷是一种广泛应用的前体药物，通过对血小板上的 P2Y 受体的不可逆抑制发挥抗血栓作用。它已获得美国食品和药物管理局（FDA）批准，可用于不稳定型心绞痛、心肌梗死、中风等血栓性疾病的临床治疗，以及经皮冠状动脉介入治疗期间的使用。肝脏代谢氯吡格雷会产生几种不同的代谢物。这些代谢物中只有一种负责抑制血小板 P2Y 受体。重要的是，已经描述了氯吡格雷治疗的各种非止血作用。这些非止血作用可能并不奇怪，因为 P2Y 受体表达已在包括成骨细胞、白细胞以及血管内皮和平滑肌在内的多种组织中被报道。虽然“无活性”代谢物通常被认为是无生物学活性的，但最近的研究发现了氯吡格雷治疗的非 P2Y 受体介导的作用，这些作用可能由研究较少的代谢物介导。在这篇综述中，我们总结了氯吡格雷及其代谢物在各种组织中通过 P2Y 受体介导和非 P2Y 受体介导的作用。
