Siguazodan (SKF 94836) is an effective, selective, orally active phosphodiesterase III ((PDE-III)) inhibitor with an IC50 of 117 nM. Siguazodan inhibited phenylephrine induced 5-HT release with an IC50 value of 4.2 μM。 Siguazodan can increase cAMP accumulation in intact platelets, with EC50 of 18.88 μM。

PDE3:117 nM

the major cyclic AMP-hydrolysing PDE in human platelet supernatantsselectively inhibited by Siguazodan . The inhibited enzyme has been variously termed cyclic GMP-inhibited PDE or PDE-III. In platelet-rich plasma (PRP), Siguazodan inhibits U46619-induced aggregation more potently than that induced by adenosine 5'-diphosphate (ADP), and collagen. In washed platelets, Siguazodan increases cyclic AMP levels and reduces cytoplasmic free calcium. ADP decreases the ability of Siguazodan to raise cyclic AMP and this may explain its lower potency in inhibiting responses to ADP. Siguazodan has anti-platelet actions over the same concentration range that it is an inotrope and vasodilator[2].

Siguazodan is a selective phosphodiesterase III inhibitor that has positive inotropic and vasodilating actions in various laboratory animals and is orally active with a long duration of action in conscious dogs[2].