PHARMACOLOGICAL PROPERTIES OF MM-706, A NEW PROSTACYCLIN DERIVATIVE

1. In human platelet-rich plasma, platelet aggregation induced in vitr o by collagen (10 mu g/ml) or thrombin (50 mU/ml) was dose-dependently inhibited by increasing concentrations of prostacyclin or of the new derivative -hexanor(1-hydroxycyclohexyl)-9a-carbaprostacyclin (MM-706) with an IC50 of 20-50 nM and 250-500 nM, respectively. In human plate lets loaded with fura-2, the intracellular rise of [Ca2+] induced by t hrombin was dose-dependently inhibited by MM-706 with an approximate I C50 of 100 mu M. 2. In rabbit isolated femoral artery, MM-706 (10 nM-1 0 mu M) was completely ineffective in relaxing the vessel, which was d ifferent to prostacyclin which was able to relax vessels at the same c oncentrations. 3. In in vitro guinea-pig ileum, prostacyclin produced a contractile effect in the concentration range 1 nM-10 mu M, but the derivative MM-706 was ineffective at the same concentrations. Preventi ve addition of MM-706 did not inhibit prostacyclin contraction. 4. On isolated guinea-pig tracheal preparation, prostacyclin induced a conce ntration-dependent contraction but the new compound MM-706 showed a lo wer activity, in the concentration range 10 nM-10 mu M. The activity o f prostacyclin was not affected by the contemporary presence of MM-706 . 5. It is concluded that MM-706 is a prostacyclin analogue with antia ggregating properties but without evident effects on smooth muscle of different regions.