Pharmacological properties of MM-706, a new prostacyclin derivative.
1. In human platelet-rich plasma, platelet aggregation induced in vitro by collagen (10 micrograms/ml) or thrombin (50 mU/ml) was dose-dependently inhibited by increasing concentrations of prostacyclin or of the new derivative (+/-)(5E)-13,14-didehydro-omega-hexanor(1-hydroxycyclo hexyl)-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 microM. 2. In rabbit isolated femoral artery, MM-706 (10 nM-10 microM) was completely ineffective in relaxing the vessel, which was different to prostacyclin which was able to relax vessels at the same concentrations. 3. In in vitro guinea-pig ileum, prostacyclin produced a contractile effect in the concentration range 1 nM-10 microM, but the derivative MM-706 was ineffective at the same concentrations. Preventive addition of MM-706 did not inhibit prostacyclin contraction. 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 10 nM-10 microM. The activity of prostacyclin was not affected by the contemporary presence of MM-706. 5. It is concluded that MM-706 is a prostacyclin analogue with antiaggregating properties but without evident effects on smooth muscle of different regions.
Ragazzi
E
E
Department of Pharmacology, University of Padova, Italy.
Chinellato
A
A
Lille
U
U
Lopp
M
M
Doni
M G
MG
Fassina
G
G
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005263:Femoral Artery / Q000187:drug effects; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects*; D011817:Rabbits; D014132:Trachea / Q000187:drug effects
C081773:MM 706; D011464:Epoprostenol; D002118:Calcium