New developments on thromboxane and prostacyclin modulators part II: prostacyclin modulators.
Prostacyclin (PGI(2)) is a potent endogenous inhibitor of platelet function and possesses a strong vasodilator effect. Furthermore, prostacyclin is currently presented as the physiologic antagonist of thromboxane A(2)(TXA(2)), which exhibits pro-aggregatory and vasoconstrictor properties. So, the balance between PGI(2) and TXA(2) production is crucial for the cardiovascular system. Indeed, an imbalance in the production or effect of these products is deleterious for the circulatory system and can lead to characterized vascular diseases such as hypertension, stroke, atherosclerosis or myocardial infarction. Although the biological effects of PGI(2) are considered to be clinically useful, its use as therapeutic agent is largely limited by both its chemical and metabolic instability. Actually, several prostacyclin agonists have been synthesized and pharmacologically evaluated. Among these, some have been clinically evaluated as therapeutic agents in several vascular diseases. This review focuses on the latest chemical and pharmacological developments in the field of the prostacyclin agonists.
de Leval
Xavier
X
Natural and Synthetic Drugs Research Center, Department of Medicinal Chemistry, University of Liège, B-4000, Liège, Belgium. xdeleval@ulg.ac.be
Hanson
Julien
J
David
Jean-Louis
JL
Masereel
Bernard
B
Pirotte
Bernard
B
Dogné
Jean-Michel
JM
D002319:Cardiovascular System / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D011464:Epoprostenol / Q000819:agonists / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors / Q000502:physiology; D013931:Thromboxanes / Q000037:antagonists & inhibitors* / Q000502:physiology
D004791:Enzyme Inhibitors; D013931:Thromboxanes; D013928:Thromboxane A2; D011464:Epoprostenol