HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Beneficial effects of combined thromboxane synthase inhibition/receptor blockade with CGS 22652 in a canine model of coronary thrombosis.

Abstract
Various antiplatelet agents were examined for their effectiveness as adjuncts to thrombolytic therapy in a canine model of thrombin-induced coronary thrombosis. Aspirin (5 mg/kg i.v. bolus), CGS 15435A (thromboxane synthase inhibitor (TxSI), 0.1 mg/kg i.v. bolus +0.04 mg/kg per h) and BM 13.505 (thromboxane receptor antagonist (TxRA), 0.5 mg/kg i.v. bolus +0.2 mg/kg per h) administered concurrently with streptokinase (750,000 units/h) were examined for their effects on reperfusion and reocclusion, as were a combination therapy with CGS 15435A + BM 13.505 or the dual TxRA/TxSI inhibitor, CGS 22652 (1 mg/kg i.v. bolus +0.4 mg/kg per h). All dogs received heparin (150 U/kg bolus + 50 U/kg per h) throughout the experimental protocol. Survival analysis at reperfusion indicated that thrombolysis was significantly improved in dogs treated with CGS 15435A, BM 13.505, CGS 15435A+BM 13.505 or CGS 22652 over that of vehicle-treated animals. Both dual inhibitor groups and the BM 13.505 group were significantly different from aspirin. Aspirin-treated dogs were not different from vehicle. Otherwise, all treatments differed from the vehicle-treated group at reocclusion. Time and incidence of reocclusion for CGS 22652 was significantly improved over that of BM 13.505. Residual thrombus weight was significantly reduced in the CGS 22652-treated and BM 13.505 + CGS 15435A-treated animals. These findings demonstrate that streptokinase-induced thrombolysis is accompanied by TxA2/prostaglandin H2 synthesis and platelet activation and suggest a role for platelet activation during reocclusion following clot lysis. These studies also show it is possible to combine the beneficial effects of both a TxRA and TxSI into a single chemical entity, CGS 22652, which, when administered as adjunctive therapy to streptokinase, results in an apparent synergistic antithrombotic effect.
AuthorsR W Olson, R Dotson, J Mathis, D S Cohen, R L Webb
JournalEuropean journal of pharmacology (Eur J Pharmacol) Vol. 236 Issue 1 Pg. 75-87 (May 12 1993) ISSN: 0014-2999 [Print] Netherlands
PMID8319746 (Publication Type: Journal Article)
Chemical References
  • Caprylates
  • Indoles
  • Phenylacetates
  • Platelet Aggregation Inhibitors
  • Pyridines
  • Receptors, Thromboxane
  • Sulfonamides
  • Thromboxanes
  • 5-chloro-1-methyl-2-(3-pyridyl)-3-indolehexanoic acid
  • CGS 22652
  • Thromboxane B2
  • 6-Ketoprostaglandin F1 alpha
  • Streptokinase
  • Thromboxane-A Synthase
  • Dinoprostone
  • Aspirin
  • daltroban
Topics
  • 6-Ketoprostaglandin F1 alpha (pharmacology)
  • Animals
  • Aspirin (therapeutic use)
  • Caprylates (therapeutic use)
  • Coronary Circulation (drug effects)
  • Coronary Thrombosis (drug therapy, physiopathology)
  • Dinoprostone (metabolism)
  • Dogs
  • Hemodynamics (drug effects)
  • Indoles (pharmacology)
  • Male
  • Myocardial Reperfusion
  • Phenylacetates (therapeutic use)
  • Platelet Activation (drug effects)
  • Platelet Aggregation Inhibitors (therapeutic use)
  • Pyridines (therapeutic use)
  • Receptors, Thromboxane (antagonists & inhibitors)
  • Streptokinase (therapeutic use)
  • Sulfonamides (therapeutic use)
  • Thromboxane B2 (pharmacology)
  • Thromboxane-A Synthase (antagonists & inhibitors)
  • Thromboxanes (antagonists & inhibitors)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: