Vascular relaxing activity and stability studies of 10,10-difluoro-13,14-dehydroprostacyclin.
10,10-Difluoro-13,14-dehydroprostacyclin was compared with natural prostacyclin (prostaglandin I2, PGI2) for vascular relaxing activity in vitro on helical strips of small canine mesenteric arteries (outside diameter < 1 mm) and bovine coronary arteries (outside diameter 1.5-2.5 mm) partially contracted with prostaglanding F2 alpha as well as in vivo in pentobarbital-anesthetized dogs. The difluoro analog was 3- to 4-fold more active than PGI2 in causing relaxation of both types of strips and appeared at least equipotent to PGI2 in its blood pressure lowering effect in dogs. When incubated with Krebs' bicarbonate solution (pH 7.4) at 37 degrees C, the biological half-life of the difluoro analog was about 24 hr compared to the 10- to 15-min half-life of PGI2 under similar conditions. However, when administered intravenously to dogs, the hemodynamic effects of the difluoro analog were of the same duration as those of PGI2.
D000818:Animals; D001158:Arteries; D001794:Blood Pressure / Q000187:drug effects; D002417:Cattle; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000494:pharmacology* / Q000031:analogs & derivatives; D066298:In Vitro Techniques; D008297:Male; D011453:Prostaglandins / Q000494:pharmacology*; D011460:Prostaglandins F / Q000037:antagonists & inhibitors; D011465:Prostaglandins, Synthetic / Q000138:chemical synthesis / Q000494:pharmacology*; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects*
D011453:Prostaglandins; D011460:Prostaglandins F; D011465:Prostaglandins, Synthetic; C024526:10,10-difluoro-13-dehydroprostacyclin; D011464:Epoprostenol