Inhibitor thromboxane

Gresele P, Dedomyn H, Amout J, N nci GG, V rmyl n J. Characterization of N,N -t>is(3 pioolyl)-4-methoxy-isophthalamide (piootamide) as a dual thromboxane synthase inhibitor/thromboxane A2 receptor antagonist in human platelets. HircmibHaemost 1989 61 479-84... 

REDUCTASE INHIBITORS DOPA-DECARBOXYLASE INHIBITORS DOPAMINE P-HYDROXYLASE INHIBITORS ENDOPEPTIDASE INHIBITORS HMG-COA REDUCTASE INHIBITORS NEUTRAL ENDOPEPTIDASE INHIBITORS NITRIC OXIDE SYNTHASE INHIBITORS PHOSPHOLIPASE INHIBITORS 5a-REDUCTASE INHIBITORS REVERSE TRANSCRIPTASE INHIBITORS THROMBOXANE SYNTHASE... 

Gresek. P. era/. (1991) Thromboxane synthase inhibitors, thromboxane receptor antagonists and dual blockers in thrombotic disorders. Trends Pharmacol Sci., 12.158-163. 

Phospholipase inhibitors Thromboxane synthetase inhibitors Prostacyclin... 

COX-2 synthesises PGI2 (prostacyclin) and the high incidence of myocardial infarctions with selective COX-2 inhibitors has been attributed to inhibition of COX-2 in vascular tissues. Prostacyclin, made by blood vessel walls, inhibits aggregation of platelets and maintains a balance with thromboxane. Thromboxane, which is released by platelets, promotes clotting. Prostacyclin is synthesised mostly by COX-1, but in humans selective COX-2 inhibition reduces its biosynthesis in vivo. This reduced synthesis may lead to an overactive thromboxane system and increased risk of thromboembolism. 

The advent of COX-2-selective inhibitors has led to unexpected results. By selectively inhibiting the COX-2 isoform, COX-2-selective NSAIDs increase the risk of cardiovascular events in certain patientsP COX-2 is responsible for the production of prostacyclin, a vasodilatory and antiplatelet substance. On the other hand, COX-1 controls the production of thromboxane A2, a vasoconstrictor and platelet aggregator. Selective inhibition of COX-2 results in decreased prostacyclin levels in the face of stable thromboxane A2 levels. An imbalance in the thromboxane A2 prostacyclin ratio ensues, which creates an environment that favors thrombosis. 

Cyclooxygenase Inhibitors. The synthesis of prostaglandin and thromboxane has been linked with multiple organ failure in animals and humans with sepsis. Bernard et al. (B18) reported the results of a large trial of the cyclooxygenase inhibitor ibuprofen in patients with sepsis. Treatment for 48 hours with... 

The widely used platelet inhibitor aspirin or acetylsalicylic acid, by acetylating the enzyme cyclooxygenase, inhibits platelet function by preventing the formation of thromboxane A2 and the synthesis of prostaglandin I2 (PGI2) (68). Aspirin has been used in combination with other antiplatelet agents such as ticlopidine, which inhibits ADP-induced platelet aggregation (69). 

Drugs that target other sites of platelet action include thromboxane synthetase inhibitors, serotonin or 5-hydroxytryptamine (5-HT2) receptor blockers, and thromboxane A2 receptor blockers, in addition to cyclooxygenase inhibitors and prostaglandin analogues. 

Banerjee AK, Peters TJ Experimental nonsteroidal anti-inflammatory drug-induced enteropathy in the rat Similarities to inflammatory bowel disease and effect of thromboxane synthetase inhibitors. Gut 1990 3 i 1358— 1364. 

Tokiyoshi K, Ohnishi T, Nii Y. 1991. Efficacy and toxicity of thromboxane synthetase inhibitor for cerebral vasospasm after subarachnoid hemorrhage. Surg Neurol 36 112-118. 

Uyama O, Nagatsuka K, Nakabayashi S, Isaka Y, Yoneda S, et al. 1985. The effect of a thromboxane synthetase inhibitor, OKY-046, on urinary excretion of immunoreactive thromboxane B2 and 6-keto-prostaglandin El alpha in patients with ischemic cerebrovascular disease. Stroke 16 241-244. 

Dogne, J. M., de Leval, X., Benoit, P., RoUn, S., Pirotte, B., and Masereel, B. (2002) Therapeutic potential of thromboxane inhibitors in asthma. Expert Opin. Investig. Drugs. 11, 275-281. 

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