Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to determine if idazoxan, an alpha 2-adrenergic antagonist, could enhance the antithrombotic activity of pelrinone, a PDE III inhibitor, in a canine model of coronary thrombosis that uses electrical current to injure the coronary endothelium. Thrombus mass in vehicle-treated animals was 37.9 +/- 8 mg. Pelrinone, 0.625 and 2.5 mg/kg decreased thrombus size by 46 and 21%, respectively, while idazoxan, 0.75 mg/kg decreased thrombus mass by 43%. When this dose of idazoxan was combined with pelrinone, 0.625 and 2.5 mg/kg, thrombus mass was decreased by 71 and 91%, respectively. Antithrombotic efficacy correlated with the ability of these treatments to inhibit epinephrine-sensitized, collagen-induced platelet aggregation. Sixty minutes following drug administration, idazoxan, 0.50 mg/kg inhibited aggregation by 50%, while pelrinone, 0.625 and 2.5 mg/kg inhibited aggregation by 55 and 68%, respectively. Combined administration of idazoxan with pelrinone, 0.625 and 2.5 mg/kg resulted in 80 and 95% inhibition of aggregation, respectively. Similar trends in inhibiting platelet aggregation to epinephrine-sensitized ADP and arachidonic acid were also observed. Experimental treatments did not affect hematocrit or circulating platelet count, although pelrinone was observed to prolong prothrombin time slightly. To examine the effect of drug-induced increases in coronary blood flow on thrombus formation, the potassium channel activator drug cromakalim was studied at a dose (0.1 mg/kg) that increased coronary blood flow by 25-35 ml/min above baseline in sham control animals. Animals treated with cromakalim showed a shorter time to coronary occlusion (103 +/- 11 min) vs. vehicle (173 +/- 24 min) and developed larger thrombi (53.7 +/- 19 mg). These results demonstrate that coronary vasodilation does not contribute to antithrombotic activity in this model. Results from the study also show that alpha-adrenergic inhibition of platelet function can potentiate phosphodiesterase inhibitor antiaggregatory and antithrombotic activity.
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PMID:Antithrombotic activity of the phosphodiesterase III inhibitor pelrinone in a canine model of coronary artery thrombosis: enhancement of efficacy with concurrent alpha 2-adrenergic antagonism. 172 88

Thrombus formation in the carotid artery is one of the common causes of transient ischemic attacks and stroke. Platelet aggregation seems to be an essential component in these processes. The present study was conducted to determine the ability of cilostazol, a phosphodiesterase III inhibitor, to prevent formation of totally occlusive thrombus in a porcine carotid artery, in comparison with ticlopidine. Castrated male Yorkshire pigs were allocated to control (n=8), cilostazol (30 mg/kg, twice a day [b.i.d] for 2 days, n=8), and ticlopidine (50 mg/kg, b.i.d. for 3 days, n=7) groups. The endothelium of the right common carotid artery was injured with electrical stimulation (150 microA) without constriction and blood flow in this region was monitored by Doppler flow probe. Arterial blood was sampled during electrical stimulation for the measurement of platelet aggregation. Total occlusion rates within 240 minutes were 87.5% (7:8), 37.5% (3:8), and 85.7% (6:7) in the control, cilostazol, and ticlopidine groups, respectively. Compared with the control group, the time to total occlusion was significantly prolonged in the cilostazol group, but not in the ticlopidine group. Consistently, platelet aggregation was significantly inhibited only in the cilostazol group. Because ticlopidine increases blood flow in the intact carotid artery before injury to a greater extent than cilostazol, direct antiplatelet action is thought to be responsible for cilostazol's beneficial effect in preventing thrombotic occlusion. These results suggest that cilostazol may be useful for the inhibition of the thrombus formation in the carotid artery and for the prevention of cerebral ischemic events.
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PMID:Effect of cilostazol, a phosphodiesterase III inhibitor, on experimental thrombosis in the porcine carotid artery. 1059 28