The venous antithrombotic profile of naroparcil in the rabbit.

Abstract

The venous antithrombotic profile of naroparcil or (4-[4-cyanobenzoyl]-phenyl)-1.5-dithio-beta-D-xylopyranoside was investigated in the rabbit following single i.v. and oral administration. Naroparcil attenuated thrombus development in a Wessler stasis model of venous thrombosis (jugular vein) employing bovine factor Xa as a thrombogenic stimulus giving ED50 values of 21.9 mg/kg and 36.0 mg/kg after respectively i.v. and oral administration. Venous antithrombotic activity was maximal 2-3 h after i.v. administration and 4-8 h after oral administration. Four hours after the oral administration of maximal antithrombotic (Wessler model, factor Xa) doses (100 and 400 mg/kg), naroparcil had no significant effect on bleeding time. In platelet poor plasma obtained from animals treated 4 h previously with various doses (25 to 400 mg/kg) of naroparcil, there was no detectable anti-factor Xa nor antithrombin activity. Similarly, naroparcil had no effect on APTT nor on thrombin time. A sensitized thrombin time (to about 35 s) was modestly but significantly increased following oral administration of the compound at 400 mg/kg. However, thrombin generation by the intrinsic pathway was reduced in a dose-related manner, maximal reduction being 65% at 400 mg/kg. The same dose of naroparcil enhanced the formation of thrombin/heparin cofactor II complexes at the expense of thrombin/antithrombin III complexes in plasma incubated with (125I)-human alpha-thrombin and induced the appearance of dermatan sulfate-like material in the plasma of treated rabbits, as measured by a heparin cofactor II-mediated thrombin inhibition assay.(ABSTRACT TRUNCATED AT 250 WORDS)

• Authors: J Millet, J Theveniaux, N L Brown
• Journal: Thrombosis and haemostasis (Thromb Haemost) Vol. 72 Issue 6 Pg. 874-9 (Dec 1994) ISSN: 0340-6245 [Print] Germany
• PMID: 7740457 (Publication Type: Journal Article)

Chemical References

• Antithrombins
• Thioglycosides
• naroparcil

Topics

• Administration, Oral
• Animals
• Antithrombins (pharmacology)
• Blood Coagulation (drug effects)
• Hemorrhage (chemically induced)
• Jugular Veins
• Male
• Partial Thromboplastin Time
• Rabbits
• Thioglycosides (pharmacology)
• Thrombin Time
• Thrombosis (prevention & control)