New Trends in Thromboxane and Prostacyclin Modulators

Thromboxane A 2 (TXA 2 ) and prostacyclin (PGI 2 ) are two labile products formed from arachidonic acid by the way of cyclooxygenase. An overproduction of thromboxane A 2 has been detected in a series of diseases whereby this prostanoid is assumed to contribute to the underlying pathomechanisms by its potent stimulation of platelet aggregation and smooth muscle contraction. This increased TXA 2 biosynthesis is frequently accompanied by a stimulation of prostacyclin formation which is one of the most potent inhibitors of platelet aggregation and smooth muscle contraction. Therefore, TXA 2 prostaglandin endoperoxide H 2 receptor antagonists, thromboxane synthase inhibitors and drugs which combine both activities have been developed with the aim to suppress the formation and/or the action of thromboxane A 2 . Since prostacyclin has been demonstrated to counterbalance the pathological effects of TXA 2 , several PGI 2 agonists have also been developed. This review will highlight the evolution and some of the latest findings in the field of prostacyclin and thromboxane A 2 modulators mainly those which are under clinical evaluation or marketed.