In vitro studies of a new synthetic thrombin inhibitor

David Green*, Chung hsin Ts'ao, Nancy Reynolds, David Kahn, Helga Kohl, Isaac Cohen

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

(2R, 4R)4-methyl-l-[Nα-(3-methyl-1, 2, 3, 4-tetrahydro-8-quinoline-sulfonyl)-L-arginyl]-2-piperidine carboxylic acid monohydrate (MCI-9038) was found to be a potent synthetic inhibitor of thrombin. In concentrations as low as 1 μM, the thrombin time, prothrombin time, and partial thromboplastin time were more than doubled. The venom (Bothrops atrox) time was similarly prolonged. The drug also inhibited the thrombin-induced activation of factors VIII and XIII. While MCI-9038 in concentrations of 10-4 M had no effect on platelet aggregation induced by collagen, ADP, epinephrine, and arachidonate, nanomolar concentrations inhibited thrombin-induced platelet aggregation and the release of platelet ADP. The drug also significantly inhibited the adhesion of thrombin-treated platelets to cultured bovine aortic endothelial cells. We conclude that MCI-9038 is an extremely potent inhibitor of the effects of thrombin on platelets and clotting factors.

Original languageEnglish (US)
Pages (from-to)145-153
Number of pages9
JournalThrombosis Research
Volume37
Issue number1
DOIs
StatePublished - Jan 1 1985

Keywords

  • Anticoagulant
  • Heparin
  • Thrombin Inhibitor

ASJC Scopus subject areas

  • Hematology

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