Vasorelaxant effect of isocarbacyclin methyl ester incorporated into lipid microspheres on isolated canine arteries.
TTC-909 is a preparation of isocarbacyclin methyl ester (CAS 88931-51-5, TEI-9090) incorporated into lipid microspheres. The characteristics of vasorelaxation induced by TTC-909 were investigated in isolated canine arteries. TTC-909 produced concentration-dependent relaxation of prostaglandin F2a(PGF2a)-induced and U-46619 (TXA2 receptor agonist)-induced contraction in basilar, coronary, renal, mesenteric, and femoral arteries. The vasorelaxant potency of TTC-909 was compared with the potencies of TEI-9090, TEI-7165 (CAS 88911-35-7, free acid of TEI-9090), prostaglandin I2 (PGI2), and prostaglandin E1 (PGE1) on PGF2a-induced contraction in basilar and femoral arteries. The relaxing potency of TTC-909 was similar to the values for TEI-9090, TEI-7165, and PGI2, and more potent than that of PGE1 in both of these arteries. An esterase inhibitor, diisopropyl fluorophosphate (DFP), reduced the vasorelaxant effect of TEI-9090, but not that of TEI-7165, on PGF2a-induced contraction in femoral arteries. These results suggest that TTC-909 has vasorelaxant potency similar to that of PGI2 and greater than that of PGE1. Further, it appears that TEI-9090 was converted to TEI-7165 by esterase and then produced its vasorelaxing effect.
D000818:Animals; D001158:Arteries / Q000187:drug effects; D004285:Dogs; D004337:Drug Carriers; D011464:Epoprostenol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D004950:Esterases / Q000037:antagonists & inhibitors; D005260:Female; D066298:In Vitro Techniques; D008081:Liposomes; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
D004337:Drug Carriers; D008081:Liposomes; D011448:Prostaglandin Antagonists; C068518:TTC 909; D014665:Vasodilator Agents; C052840:TEI 9090; C041946:9-O-methanoprostaglandin I; D011464:Epoprostenol; D004950:Esterases