The thromboxane receptor antagonist, BAY U3405, prevents arterial thrombosis, but not rethrombosis, in a canine model

1992 ◽  
Vol 24 ◽  
pp. S65
Author(s):  
W ROTE
1993 ◽  
Vol 23 (4) ◽  
pp. 219-228
Author(s):  
W.A. Schumacher ◽  
C.L. Heran ◽  
S. Youssef ◽  
J.R. Megill ◽  
I. Michel ◽  
...  

1993 ◽  
Vol 70 (05) ◽  
pp. 822-825 ◽  
Author(s):  
B Hoet ◽  
J Arnout ◽  
H Deckmyn ◽  
J Vermylen

SummaryRidogrel, a combined thromboxane receptor antagonist and thromboxane synthase inhibitor (1), inhibits platelet aggregation. Following stimulation with arachidonic acid, cAMP-levels are increased in human platelets preincubated with ridogrel, this is due to the known reorientation of the metabolism of the formed endoperoxides towards adenylate cyclase stimulating prostaglandins.Pretreatment of resting platelets with UDCG-212, a cAMP-phosphodiesterase inhibitor (2), also inhibits platelet aggregation induced by arachidonic acid, concomitant with an increase in cAMP levels, due to an inhibition of its breakdown. Under basal conditions, cAMP also is increased.By combining the two drugs, a more than additive action was observed on platelet aggregation and on both resting and stimulated platelet cAMP content. The appropriate combination may result in a more effective antiplatelet strategy.


1993 ◽  
Vol 69 (05) ◽  
pp. 509-514 ◽  
Author(s):  
W A Schumacher ◽  
T E Steinbacher ◽  
C L Heran ◽  
J R Megill ◽  
S K Durham

SummaryThese studies describe experimental conditions where aspirin is less effective than other antiplatelet and anticoagulant drugs in inhibiting acute arterial thrombosis. External electrolytic injury of the rat carotid artery was used to induce occlusive thrombi in 97% of vehicle-treated rats. Thrombi were revealed by light and electron microscopy to be comprised primarily of platelets enmeshed in a fibrin network. The thrombin inhibitor D-phenylalanyl-L-prolyl-L-arginyl chloromethy ketone (PPACK; 6 mg/kg, i. v.) decreased thrombus weight by 90%. Aspirin alone (1, 10 and 30 mg/kg, i. v.), dipyridamole alone (5 mg/kg i. v.) and aspirin (1 and 10 mg/kg, i. v.) in combination with dipyridamole (5 mg/kg, i. v.) did not inhibit thrombosis. The platelet-activating factor (PAF) antagonist, WEB 2086, (1 mg/kg i. v.) was also ineffective. Other drugs had intermediate activity. Thrombi were decreased 56% by the thromboxane receptor antagonist, BMS 180,291, either alone (5.8 mg/kg i.v.) or in combination with aspirin (10 mg/kg, i.v.). Heparin (900 U/kg, i.v.), warfarin (0.25 mg/kg, p.o. once daily for 3 days) and ticlopidine (200 mg/ kg, p.o. once daily for 3 days) reduced thrombus weight by 63, 73 and 43% respectively. Reductions in thrombus weight were always associated with improvements in either average blood flow or vessel patency.


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