Picotamide : An inhibitor of the formation and effects of TxA2

After the discovery of thromboxane A, (TXA,) by Hamberg in 1975 (31), considerable efforts have been made to find a drug therapy to control its biological effects. Platelets produce a considerable amount of TXA, during aggregation and are involved in thromboembolic diseases. Early antithrombotic and antiTXA, therapies were viewed as antiplatelet treatments, and the cyclooxygenase inhibitors, particularly aspirin, became the drugs of choice for antithrombotic therapy. The usefulness of these drugs was limited because they do not specifically block TXA,. Thus, a more specific and effective drug to inhibit TXA, was sought. Another compelling reason to develop new specific and effective TXA, inhibitors was the discovery that many cells in addition to platelets, such as monocyte-macrophages, endothelial, and vascular muscle cells (44,55,63), synthesize and release TXA,. Even cells that do not synthesize TXA, at rest may express cyclooxygenase and synthesize TXA, when stimulated by inflammatory cytokines (67). Thus, TXA, may represent an important mediator of different inflammatory processes: it has diverse biological effects, including contraction of vascular and pulmonary smooth muscle, lysis of cell membranes, and promotion of leucocyte adhesion. As a consequence, TXA, may play a role not only in platelet aggregation but also in renal disease, chronic bowel disease and various cardiovascular disorders, including coronary artery disease. Because of the possible wide-ranging effects of TXA,, the search for effective inhibitors of TXA, has been expanded. These inhibitors are being investigated as part of a general treatment strategy to be used in several diseases where increased TXA, formation plays a pathophysiological role. Two specific antiTXA, approaches were initially proposed: inhibition of TXA, synthase and inhibition of TXA, receptors, but in clinical trials neither approach offered any