Treatment of thrombotic diseases implicates the use of anti-platelet agents, anti-
coagulants and pro-fibrinolytic substances. Amongst the anti-platelet drugs,
aspirin occupies a unique position. As soon as it became evident that the major action of
aspirin is indirect blockade, through inhibition of
cyclooxygenase (COX), of the production of
thromboxane A2 (TXA2), a powerful
vasoconstrictor and platelet activator, research for new anti-thrombotics that interact more specifically with the production and/or the action of TXA2 was started.
Terutroban (S 18886) is a selective antagonist of
TP receptors, the receptors for TXA2, that are present on platelets and on vascular smooth muscle cells, but also on endothelial cells. The role played by the platelet and smooth muscle cell
TP receptors in thrombotic disease is well known, and preclinical and clinical studies with
terutroban have illustrated the powerful antithrombotic effects of this agent. The implication of endothelial
TP receptors in the development of atherosclerotic disease has only been examined during the past five years and studies with
terutroban have been crucial for understanding the role of these endothelial receptors in cardiovascular physiopathology. The goal of the present review is to discuss the arguments in favour of the hypothesis suggesting that activation of endothelial
TP receptors, by causing expression of adhesion molecules, favours adhesion and infiltration of monocytes/macrophages in the arterial wall, thereby stimulating the development of
atherosclerosis. The review will also highlight the important contribution of the studies performed with
terutroban in this research area. The triple activity (anti-thrombotic, anti-
vasoconstrictor, anti-atherosclerotic) observed with
terutroban in preclinical studies, stressed by the first results in clinical development, places
terutroban as an innovative
drug with a unique potential for treatment of cardiovascular disorders.