The pharmacodynamics of antiplatelet compounds in thrombosis treatment

ABSTRACT

Introduction: As it is importance to understand the involvement of platelets in the initiation and propagation of thrombosis, antiplatelet drugs have come to the forefront of atherothrombotic disease treatment. Dual antiplatelet therapy of aspirin plus clopidogrel has its benefits, but it also has its limitations with regard to its pharmacologic properties and adverse effects. For these reasons, within the last decade or so, the investigation of novel antiplatelet agents has prospered.

Areas covered: In this review, we discuss the unique pharmacodynamic properties of several antiplatelet drugs with their possible potential molecular of mechanisms on inhibiting platelet aggregation.

Expert opinion: Considering multiple synergetic pathways of platelet activation and their close interplay with coagulation, the current treatment strategies are not only based on platelet inhibition, they also rely on the attenuation of procoagulant activity, inhibition of thrombin generation, and enhancement of clot dissolution. Current guidelines recommend various antiplatelet agents in addition to aspirin for patients with acute coronary syndromes. The advantages of these agents, as repute mortality, may be associated with off-target effects of the drug. Hence, further studies are required to facilitate the physician’s choice of the most appropriate antiplatelet agents for each patient for thrombosis treatment.

KEYWORDS:

• Antiplatelets
• pharmacodynamics
• antithrombotic
• multi-targets

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Article highlights

• Natural antiplatelet agents such as tetramethylpyrazine, kinetin, rutin, lycopene, C-phycocyanin, caffeic acid phenethyl ester, resveratrol, sesamol, andrographolide, sulforaphane, xanthohumol, hinokitiol, and CME-1 inhibit platelets aggregation via multiple targets.

• Endogenous antiplatelet compounds, include metallothionein andmatrix metalloproteinase possess significant antiplatelet effects via inhibiting the activation of PLC, PKC, PI3 breakdown, TxA2 formation, and inhibition of intracellular Ca²⁺mobilization. They also increased cAMP levels.

• Inhibitory effect of endogenous antiplatelet compounds was also accompanied by inhibiting OH^○ formation in vitro and increasing the latency period for inducing platelet plug formation in vivo.

• Clinically used and P2Y12 and GP IIb/IIIa antagonists holds potent antiplatelet effects via suppressing p38 MAPK, ERK phosphorylation. This effect was also convoyed by increasing cAMP, cGMP, NO release, VASP phosphorylation, and eNOS expression.

• This review may provide a useful preventive approach or an adjunct to current pharmacological treatments for thrombotic diseases.

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Declaration of interest

This work was supported by grants from the National Science Council of Taiwan (NSC97-2320-B-038-016-MY3 and NSC100-2320-B-038-021-MY3), the Cathay General Hospital-Taipei Medical University (103CGH-TMU-06; CGH-MR-A10308), and Wan-Fang Hospital-Taipei Medical University (102TMU-WFH-02-2). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.