ABSTRACT
The discovery of thromboxane A2 (TxA2) in 1975 1 and of prostacyclin (PGI2) in 1976 2 , 3 heralded a new era in prostaglandin research. 4 Indeed, one authority in the field once proposed that all previous research had been devoted to the biologically useless side products of these two agents. The elucidation of the conversion of arachidonic acid to the endoperoxides PGG2 and PGH2 (see Scheme 1), and thence to either thromboxane (especially in platelets) or prostacyclin (endothelial cells), immediately suggested the possibility of redirecting the metabolism of arachidonic acid towards prostacyclin, if specific inhibitors of thromboxane synthetase could be found. 5 , 6 It was suggested by various authors that an overproduction of thromboxane A2 (or a hypersensitivity to this agent) might be involved in such disease states as stroke, thrombus formation, angina, Raynaud's syndrome, platelet hyperaggregability, myocardial infarction, cerebral vasospasm, shock, septicemia, graft rejection, asthma, atherosclerosis, and diabetes, among others. It was also proposed 6 , 7 by Moncada and Vane that endoperoxides released by platelets were converted to the antiaggregatory prostacyclin (PGI2) by vascular walls, preventing platelet adhesion and aggregation unless injury occurred. Although it is now believed that endoperoxides are only released from platelets when thromboxane synthetase is inhibited, 8 conversion of excessive amounts of thromboxanes, produced in response to a stimulus, to the beneficial prostacyclin would offer an advantage not possible with cyclooxygenase inhibitors.** (Unfortunately, recent work seems to suggest that prostacyclin formation in vivo is not altered when thromboxane synthesis is inhibited. 10 ) Specific inhibition of thromboxane formation would seem to offer both a diagnostic tool to determine the level of involvement of thromboxane in a variety of settings, or the potential of treating various pathological states to which this agent contributed.
