Anti-thrombotic activity of KBT-3022 in experimental models of thrombosis

Jpn J Pharmacol. 1995 Jun;68(2):201-6. doi: 10.1254/jjp.68.201.

Abstract

In this study, we investigated the effects of KBT-3022 (ethyl 2-[4,5-bis(4-methoxyphenyl)-thiazol-2-yl]pyrrol-1-ylacetate) , a potent and long-lasting anti-platelet agent, in several experimental thrombosis models and compared them with those of other anti-platelet drugs. Oral administration of KBT-3022 prevented arachidonic acid-induced death due to pulmonary embolism in mice and rabbits with respective ED50 values of 0.29 and 0.12 mg/kg. The protective effect of acetylsalicylic acid (ASA) against mortality was weaker than that of KBT-3022, and ticlopidine hydrochloride (TP) showed no such effect in these models. In a guinea pig arterio-venous shunt model, the inhibition by KBT-3022 of thrombus formation on a silk thread inserted into the shunt was dose-dependent and 300 and 30 times more potent than the inhibition obtained with ASA and indomethacin, respectively. In a model of aortic thrombosis induced by perivascular application of 20% silver nitrate solution, KBT-3022 (1 mg/kg, p.o.) inhibited thrombus formation significantly, ASA (100 mg/kg, p.o.) tended to inhibit it, and TP had no effect. However, in a stasis-induced venous thrombosis model in guinea pigs, TP inhibited thrombus formation significantly, but KBT-3022 and ASA were ineffective. These results suggest that KBT-3022 may be a useful drug for the treatment and/or prophylaxis of thrombus formation in shunts and aortic thrombosis.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Arachidonic Acid
  • Aspirin / therapeutic use
  • Cyclooxygenase Inhibitors / pharmacology
  • Extracorporeal Circulation
  • Guinea Pigs
  • In Vitro Techniques
  • Indomethacin / pharmacology
  • Male
  • Mice
  • Mice, Inbred Strains
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Pyrroles / therapeutic use*
  • Rabbits
  • Silver Nitrate
  • Thiazoles / therapeutic use*
  • Thrombosis / chemically induced
  • Thrombosis / drug therapy*
  • Ticlopidine / therapeutic use

Substances

  • Cyclooxygenase Inhibitors
  • Platelet Aggregation Inhibitors
  • Pyrroles
  • Thiazoles
  • KB 3022
  • Arachidonic Acid
  • Silver Nitrate
  • Ticlopidine
  • Aspirin
  • Indomethacin