HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Antithrombotic effects in a rat model of aspirin-insensitive arterial thrombosis of desethyl KBT-3022, the main active metabolite of a new antiplatelet agent, KBT-3022.

Abstract
The antithrombotic effect of desethyl KBT-3022, which is the main active metabolite of the new antiplatelet agent, KBT-3022 (ethyl 2-[4,5-bis(4-methoxyphenyl)thiazol-2-yl] pyrrol-1-ylacetate; a cyclooxygenase inhibitor), was determined using a photochemically induced arterial thrombosis model in the rat femoral artery. Pretreatment with desethyl KBT-3022 (0.1, 0.3 and 1 mg/kg, i.v.) prolonged the time required to achieve thrombotic occlusion in the femoral artery and inhibited collagen-induced platelet aggregation in whole blood ex vivo, each in a dose-dependent manner. In all 6 rats used, particularly at the highest dose (1 mg/kg, i.v.) tested, cyclic variations in blood flow were hardly ever observed and complete cessation of blood flow did not occur during the 30-min observation time. BM-13505 (1, 3 and 10 mg/kg, i.v.), a thromboxane A2 receptor antagonist, also prolonged the time to occlusion, but cyclic variations in blood flow did occur. On the other hand, aspirin (10 and 30 mg/kg, i.v.) had little effect in terms of preventing thrombosis, although it inhibited collagen-induced platelet aggregation to the same extent as did desethyl KBT-3022. Desethyl KBT-3022 inhibited the thrombin-induced aggregation of washed platelets in a concentration-dependent manner (1-40 microM), whereas aspirin and BM-13505 did not. These findings suggest that the potent antithrombotic effect of desethyl KBT-3022 may be attributable in part to its additional ability to inhibit thrombin-induced platelet aggregation. Accordingly, thromboxane A2 and thrombin may be important thrombotic mediators in this rat model.
AuthorsM Shimazawa, Y Takiguchi, K Umemura, K Kondo, M Nakashima
JournalEuropean journal of pharmacology (Eur J Pharmacol) Vol. 328 Issue 2-3 Pg. 183-9 (Jun 11 1997) ISSN: 0014-2999 [Print] Netherlands
PMID9218700 (Publication Type: Comparative Study, Journal Article)
Chemical References
  • Phenylacetates
  • Platelet Aggregation Inhibitors
  • Pyrroles
  • Sulfonamides
  • Thiazoles
  • KB 3022
  • desethyl KB 3022
  • Aspirin
  • daltroban
Topics
  • Animals
  • Aspirin (pharmacology)
  • Femoral Artery (radiation effects)
  • Light (adverse effects)
  • Male
  • Phenylacetates (pharmacology)
  • Platelet Aggregation (drug effects)
  • Platelet Aggregation Inhibitors (pharmacology)
  • Pyrroles (pharmacology)
  • Rats
  • Rats, Wistar
  • Regional Blood Flow (drug effects)
  • Sulfonamides (pharmacology)
  • Thiazoles (pharmacology)
  • Thrombosis (drug therapy, etiology, physiopathology)

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: