Effects of CI-930 on hemostasis, thrombosis, and AA-induced hemodynamic reaction.
In mice, CI-930 0.5-2 mg.kg-1 ip not only prolonged the tail bleeding time but also protected the mice from sudden thromboembolic death induced by arachidonic acid (AA, 100 mg.kg-1, i.v.) or TXA2/PGH2 mimetic U46619 (200 micrograms.kg-1, i.v.). CI-930 0.625 and 2.5 mg.kg-1 i.v. exhibited a dose-dependent inhibitory effect on thrombus formation in rat arteriovenous shunt. All these effects of CI-930 were more potent than those of dazoxiben, a known antiplatelet drug. In rabbit, AA 0.75 mg.kg-1 i.v. caused a rapid and marked increase in pulmonary vascular resistance and a concomitant sharp decrease in cardiac output and carotid arterial pressure. CI-930 itself 0.5 mg.kg-1 i.v. resulted in a long-lasting fall in carotid arterial pressure, systemic vascular resistance, and a slight decrease in cardiac output. In addition, CI-930 protected rabbit from all the harmful hemodynamic responses to the occlusion of pulmonary microcirculation, which was induced by AA. The results suggest that CI-930 possess a potent anti-hemostatic, antithrombotic, and probably antihypertensive effects on experimental animals.
Jiang
Y Y
YY
Department of Pharmacology, College of Pharmacy, Second Military Medical University, Shanghai, China.
Fu
C D
CD
Liao
L M
LM
Huang
T G
TG
Chen
X S
XS
Long
K
K
D000818:Animals; D016718:Arachidonic Acid; D001760:Bleeding Time; D002316:Cardiotonic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D006439:Hemodynamics / Q000187:drug effects*; D006487:Hemostasis / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D011655:Pulmonary Embolism / Q000188:drug therapy; D011724:Pyridazines / Q000494:pharmacology* / Q000627:therapeutic use; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013927:Thrombosis / Q000188:drug therapy*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D002316:Cardiotonic Agents; D007093:Imidazoles; D011724:Pyridazines; C029166:dazoxiben; D016718:Arachidonic Acid; C042528:4,5-dihydro-6-(4-(imidazol-1-yl)phenyl)-5-methyl-3(2H)-pyridazinone; D013930:Thromboxane-A Synthase