A 15-nonstereogenic carbocyclic analogue of prostacyclin: effects on human platelets and uterine artery.
Platelet-suppressant and vasodilator effects of the (+) enantiomer of 13,14-dihydro-15,16,17,18,19,20-hexanor-14-(1-hydroxycyclohexyl)++ +carbocyclin (MM706), a carbocyclic analogue of prostacyclin with the 15-hydroxyl group located at a symmetrically substituted carbon atom were studied on human platelets and isolated uterine artery. In washed platelets it inhibits platelet aggregation with an IC50 value of 77 nM as compared to IC50 = 1.3 nM for PGI2. In the presence of indomethacin its potency like that of PGI2 decreases about 2-fold. Also, MM706 like PGI2 fails to inhibit the norepinephrine (NE)-stimulated contractions of isolated human uterine artery in the absence of indomethacin. Pretreatment of the artery with indomethacin (3 microM) makes it sensitive to both MM706 and PGI2, the EC50 values being 99 and 3.1 nM, respectively. The results show that MM706 is an effective inhibitor of platelet aggregation and NE-stimulated contractions of the indomethacin-treated uterine artery.
Kobzar
G
G
Institute of Chemistry, Estonian Academy of Sciences, Tallinn.
Shelkovnikov
S
S
Mardla
V
V
Savitski
G
G
Lopp
M
M
Kanger
T
T
Lille
U
U
D001158:Arteries / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects*; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D013237:Stereoisomerism; D014599:Uterus / Q000098:blood supply*; D014661:Vasoconstriction / Q000187:drug effects
C081773:MM 706; D011464:Epoprostenol; D009638:Norepinephrine