A 15-NONSTEREOGENIC CARBOCYCLIC ANALOG OF PROSTACYCLIN - EFFECTS ON HUMAN PLATELETS AND UTERINE ARTERY

Platelet-suppressant and vasodilator effects of the (+) enantiomer of ,19,20-hexanor-14-(1-hydroxycyclohexyl)carbacyclin (MM706), a carbocyc lic analogue of prostacyclin with the 15-hydroxyl group located at a s ymmetrically substituted carbon atom were studied on human platelets a nd isolated uterine artery. In washed platelets it inhibits platelet a ggregation with an IC50 value of 77 nM as compared to IC50 1.3 nM for PGI(2). In the presence of indomethacin its potency like that of PGI(2 ) decreases about 2-fold. Also, MM706 like PGI(2) fails to inhibit the norepinephrine (NE)-stimulated contractions of isolated human uterine artery in the absence of indomethacin. Pretreatment of the artery wit h indomethacin (3 mu M) makes it sensitive to both MM706 and PGI(2), t he EC(50) values being 99 and 3.1 nM, respectively The results show th at MM706 is an effective inhibitor of platelet aggregation and NE-stim ulated contractions of the indomethacin-treated uterine artery.