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  • Title: [Thromboxane antagonism in thrombocytes--pathophysiology, pharmacology and possible clinical significance].
    Author: Schrör K.
    Journal: Wien Klin Wochenschr; 1991; 103(18):543-53. PubMed ID: 1836294.
    Abstract:
    Thromboxanes are cyclooxygenase products of C-20 polyenoic fatty acids. The arachidonic acid derivate, thromboxane A2 (TXA2), is the only biologically relevant product and is mainly generated in blood platelets. Hyperreactivity of blood platelets appears to be an important risk factor for thromboembolic vessel occlusion in the presence of preexisting vascular pathology. Starting with acetylsalicylic acid, which is still the reference standard, several attempts have been made over the past few years to develop more specific drugs which selectively modify platelet TXA2 formation, a most important feedback-stimulator of platelet function. Thromboxane synthase inhibitors were the first compounds which were tested clinically. Some data suggest beneficial effects in several types of cardiovascular disease. However, the overall impression is that the compounds available so far may not be superior to acetylsalicylic acid. Thromboxane receptor antagonists and mixed type synthase inhibitor/receptor blocking compounds would appear to be more promising from a theoretical point of view. These compounds exhibit a number of beneficial effects in animal studies. However, clinical experience so far is very limited. It is concluded that fresh insight into the regulation and types of thromboxane receptors, the development of long-lasting synthase inhibitors, non-competitive thromboxane receptor antagonists and combined mode-active drugs, as well as a better understanding of interactions between several classes of platelet-active mediators (prostacyclin, nitric oxide, PAF) will probably result in improved drug treatment of ischaemic cardiovascular disease in the near future.
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