Thromboxane

Thromboxane is a member of the family of lipids known as eicosanoids. The two major thromboxanes are thromboxane A2 and thromboxane B2. The distinguishing feature of thromboxanes is a 6-membered ether-containing ring.

Thromboxane is named for its role in clot formation (thrombosis).

Production
Thromboxane-A synthase, an enzyme found in platelets, converts the arachidonic acid derivative prostaglandin H2 to thromboxane.

Mechanism
Thromboxane acts by binding to any of the thromboxane receptors, G-protein-coupled receptors coupled to the G protein Gq.

Functions
Thromboxane is a vasoconstrictor and a potent hypertensive agent, and it facilitates platelet aggregation.

It is in homeostatic balance in the circulatory system with prostacyclin, a related compound. The mechanism of secretion of thromboxanes from platelets is still unclear.

Role of A2 in platelet aggregation
Thromboxane A2 (TXA2), produced by activated platelets, has prothrombotic properties, stimulating activation of new platelets as well as increasing platelet aggregation.

Platelet aggregation is achieved by mediating expression of the glycoprotein complex GP IIb/IIIa in the cell membrane of platelets. Circulating fibrinogen binds these receptors on adjacent platelets, further strengthening the clot.

Pathology
It is believed that the vasoconstriction caused by thromboxanes plays a role in Prinzmetal's angina. Omega-3 fatty acids have higher levels of TxA,3 which is relatively less potent than TxA2 and PGI3; therefore, there is a balance shift toward vasoconstriction and platelet aggregation inhibition. It is believed that this shift in balance lowers the incidence of myocardial infarction and stroke.

Inhibitors
Thromboxane inhibitors are broadly classified as either those that inhibit the synthesis of thromboxane, or those that inhibit the target effect of it.

Thromboxane synthesis inhibitors, in turn, can be classified regarding which step in the synthesis they inhibit:
 * The widely used drug aspirin acts by inhibiting the ability of the COX enzyme to synthesize the precursors of thromboxane within platelets. Low-dose, long-term aspirin use irreversibly blocks the formation of thromboxane A2 in platelets, producing an inhibitory effect on platelet aggregation. This anticoagulant property makes aspirin useful for reducing the incidence of heart attacks. 40 mg of aspirin a day is able to inhibit a large proportion of maximum thromboxane A2 release provoked acutely, with the prostaglandin I2 synthesis being little affected; however, higher doses of aspirin are required to attain further inhibition.
 * Thromboxane synthase inhibitors inhibit the final enzyme (thromboxane synthase) in the synthesis of thromboxane. Ifetroban is a potent and selective thromboxane receptor antagonist. Dipyridamole antagonizes this receptor too, but has various other mechanisms of antiplatelet activity as well.

The inhibitors of the target effects of thromboxane are the thromboxane receptor antagonist, including terutroban.

Picotamide has activity both as a thromboxane synthase inhibitor and as a thromboxane receptor antagonist.

Terminology
Thromboxane synthetase is a misnomer for thromboxane synthase but is often found in the literature.