The antithrombotic effect of low molecular weight synthetic thrombin inhibitors, argatroban and PPACK, on He-Ne laser-induced thrombosis in rat mesenteric microvessels

Thromb Res. 1993 Jan 1;69(1):93-100. doi: 10.1016/0049-3848(93)90006-a.

Abstract

The antithrombotic effect of low molecular weight synthetic thrombin inhibitors, argatroban ((2R, 4R)-4-methyl-1-[N2-[(3-methyl-1, 2, 3, 4-tetrahydro-8-quinolinesulfonyl)-L-arginyl]-2-piperidinecarbox ylic acid monohydrate]) and PPACK (D-phenylalanyl-L-prolyl-L-arginyl-chloromethyl ketone) on He-Ne laser-induced thrombosis in rat mesenteric microvessels was studied. Both inhibitors showed a significant antithrombotic effect at 0.5 mg/kg which lasted for 50 min and 50-60 min using argatroban and PPACK, respectively. A dose-dependent effect was observed in arterioles and venules. The results suggest that thrombin plays an important role in the formation of a platelet thrombus in vivo.

MeSH terms

  • Amino Acid Chloromethyl Ketones / pharmacology*
  • Animals
  • Antithrombins / pharmacology*
  • Arginine / analogs & derivatives
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Male
  • Mesentery / blood supply
  • Microcirculation / drug effects
  • Pipecolic Acids / pharmacology*
  • Platelet Aggregation / physiology
  • Rats
  • Rats, Wistar
  • Sulfonamides
  • Thrombin / physiology
  • Thrombosis / prevention & control*

Substances

  • Amino Acid Chloromethyl Ketones
  • Antithrombins
  • Pipecolic Acids
  • Sulfonamides
  • Arginine
  • Thrombin
  • argatroban
  • phenylalanyl-prolyl-arginine-chloromethyl ketone