Current Pharmaceutical Design - Volume 9, Issue 28, 2003

Cilostazol (CLZ) was originally developed as a selective inhibitor of cyclic nucleotide phosphodiesterase 3 (PDE3). PDE3 inhibition in platelets and vascular smooth muscle cells (VSMC) was expected to provide an antiplatelet effect and vasodilation. Recent preclinical studies have demonstrated that CLZ also possesses the ability to inhibit adenosine uptake by various cells, a property that distinguishes CLZ from other PDE3 inhibit Read More

Platelet P2 receptors-P2Y1, P2Y12, and P2X1-constitute the means by which adenine nucleotides can activate platelets. Coactivation of the Gαq-coupled P2Y1 and Gαi2-coupled P2Y12 receptors is necessary for ADPmediated platelet activation, which forms the basis of using P2 antagonists as antithrombotic drugs. P2Y1 receptor antagonists inhibit platelet activation, while P2Y1 knockout mice show longer bleeding times than n Read More

Cardiovascular and cerebrovascular diseases continue to be leading causes of death throughout the world. Blood platelets play a pivotal role not only in haemostasis but also in the pathogenesis of thrombosis and atherosclerosis, platelet aggregation being an essential step in the formation of either an effective haemostatic plug or an intravascular thrombus. The benefits of various antiplatelet therapies ranging from aspirin, tic Read More

Heparin and low molecular weight heparins are major clinical anticoagulants and the drugs of choice for the treatment of deep venous thrombosis. The discovery of an antithrombin binding domain in heparin focused interest on understanding the mechanism of heparin's antithrombotic / anticoagulant activity. Various heparin-mimetic oligosaccharides have been prepared in an effort to replace polydisperse heparin and lo Read More

Coronary heart disease (CHD) is the leading cause of mortality and morbidity in the United States. Currently, there are approximately 12 million Americans with CHD, which is most frequently caused by atherosclerosis. The thrombotic complications of atherosclerosis, such as acute coronary syndrome and ischemic stroke, can be fatal and those who survive such events have a far greater risk of future cardiovascular events. T Read More

Thrombin, a plasma serine protease, plays a key role not only in coagulation and hemostasis but in thrombosis, restenosis and atherosclerosis. Thrombin activates platelets, endothelium, inflammatory cells and smooth muscle cells. The cellular action of thrombin is mediated by specific G-protein coupled thrombin receptors called proteinase-activated receptors (protease-activated receptor or PARs). Among the three thro Read More

Thrombosis is the collective term for diseases caused by the localized accumulation of circulating blood elements within the vasculature that result in vessel occlusion. Conventional antithrombotic drugs can inhibit thrombus growth by targeting coagulation pathways (e.g., heparin, warfarin) or platelet-dependent mechanisms (e.g., aspirin, clopidogrel). Thrombolytic agents (e.g., streptokinase) are used to degrade thrombi in situ Read More