PHARMACOLOGICAL PROPERTIES OF MM-706, A NEW PROSTACYCLIN DERIVATIVE

. 1. In human platelet-rich plasma, platelet aggregation induced in vitro by collagen (10 μg/ml) or thrombin (50 mU/ml) was dose-dependently inhibited by increasing concentrations of prostacyclin or of the new derivative (±)(5E)-13,14-didehydro-ω-hexanor(1-hydroxycyclohexyl)-9a-carbaprostacyclin (MM-706) with an IC50 of 20–50 nM and 250–500 nM, respectively. In human platelets loaded with fura-2, the intracellular rise of [Ca2+] induced by thrombin was dose-dependently inhibited by MM-706 with an approximate IC50 of 100 μM. 2. 2. In rabbit isolated femoral artery, MM-706 (10nM–10μM) was completely ineffective in relaxing the vessel, which was different to prostacyclin which was able to relax vessels at the same concentrations. 3. 3. In in vitro guinea-pig ileum, prostacyclin produced a contractile effect in the concentration range 1 nM-10μM, but the derivative MM-706 was ineffective at the same concentrations. Preventive addition of MM-706 did not inhibit prostacyclin contraction. 4. 4. On isolated guinea-pig tracheal preparation, prostacyclin induced a concentration-dependent contraction but the new compound MM-706 showed a lower activity, in the concentration range 10nM–10μM. The activity of prostacyclin was not affected by the contemporary presence of MM-706. 5. 5. It is concluded that MM-706 is a prostacyclin analogue with antiaggregating properties but without evident effects on smooth muscle of different regions.