Platelet activation, and antiplatelet targets and agents: current and novel strategies.
Platelets play a key role in thrombosis and haemostasis, which can be either beneficial or deleterious depending on the circumstances. Multiple factors, such as genetic polymorphisms, pathological state and lifestyle, are thought to be associated with platelet hyperreactivity. Platelet activation occurs through the complex process of transmembrane signalling, with a cascade of biochemical interactions leading to platelet activation. Transmembrane signalling involves many different molecules with different enzymatic activity and/or function. Based on the signalling pathways involved in platelet activation, there are four possible targets of antiplatelet drugs: (i) inhibition of agonist generation; (ii) receptor inhibition; (iii) G-protein inhibition; and (iv) inhibition of enzymatic cascades. However, both established and novel antiplatelet drugs have their own advantages and disadvantages. Because of the problems associated with the use of current antiplatelet drugs, such as resistance, optimal dosage and safety, future strategies for the development of new antiplatelet drugs and new treatment regimens may include consideration of the following: (i) a shift from single targets within the signalling cascade to multiple targets; (ii) a shift from therapy with a single drug to combination therapy; and (iii) investigating drugs in current clinical use for novel antiplatelet properties.
Xiang
Yao-Zu
YZ
Research Center of Tianjin University of Traditional Chinese Medicine, Tianjin, China. xiangyaozu@gmail.com
Xia
Ye
Y
Gao
Xiu-Mei
XM
Shang
Hong-Cai
HC
Kang
Li-Yuan
LY
Zhang
Bo-Li
BL
D015195:Drug Design; D006801:Humans; D015201:Meta-Analysis as Topic; D008954:Models, Biological; D015539:Platelet Activation / Q000187:drug effects* / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D016032:Randomized Controlled Trials as Topic; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
D010975:Platelet Aggregation Inhibitors