Prostacyclin-stimulating drugs: new prospects.
SKF 525-A (proadifen), a well-known inhibitor of drug metabolism and cytochrome P-450 activity, stimulated the release of prostacyclin (PGI2) from the rabbit aorta in vitro. The PGI2-stimulating activity of SKF 525-A was characterized by specific structural requirements: activity was abolished by the deletion of the terminal propyl chain and increased by its elongation into an isobutyl chain; chlorination of the phenyl rings increased the potency. SKF 525-A increased the production of PGI2 by cultured endothelial cells from bovine aorta and human umbilical vein, but had no effect on cultured smooth muscle from the bovine aortic media. In human platelets, SKF 525-A inhibited prostaglandin and thromboxane production induced by A23187, thrombin and ADP. Simultaneous stimulation of endothelial PGI2 and inhibition of platelet TxA2 represents an original pharmacological profile: SKF 525-A might thus constitute the prototype of a new class of antiplatelet drugs.
D000818:Animals; D001011:Aorta / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D011464:Epoprostenol / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D011335:Proadifen / Q000031:analogs & derivatives* / Q000494:pharmacology*; D011453:Prostaglandins / Q000096:biosynthesis*; D011817:Rabbits; D013329:Structure-Activity Relationship; D014471:Umbilical Veins / Q000378:metabolism
D011453:Prostaglandins; D011335:Proadifen; D011464:Epoprostenol