The antithrombotic effect of synthetic low molecular weight human factor Xa inhibitor, DX-9065a, on He-Ne laser-induced thrombosis in rat mesenteric microvessels.

Abstract

The effect of a synthetic low molecular weight factor Xa (FXa) inhibitor, DX9065a, on thrombosis in vivo were examined in a rat animal model using a Helium-Neon (He-Ne) laser method. DX-9065a administered either intravenously or orally promoted anti factor Xa activity in a dose dependent manner. Anti Xa activity was maximal immediately after intravenous injection and persisted for approximately 30 minutes. Inhibitory activity was maximal 15-30 minutes after oral administration and persisted for approximately 90 minutes. Similarly DX-9065a inhibited platelet-rich thrombosis formation in mesenteric arterioles and venules. In these instances inhibition was relatively transient after intravenous injection (10-20 minutes), but persisted for more than 3 hours after oral administration. The minimum effective doses of DX-9065a given intravenously and orally were 3.89 mg/kg and 25.9 mg/kg, respectively. The results confirmed that DX-9065a selectively modulates thrombotic mechanisms, and suggest that development of this synthetic FXa antagonist could constitute an effective intravenous and oral antithrombotic agent.

• Authors: T Yamashita, T Tsuji, A Matsuoka, J C Giddings, J Yamamoto
• Journal: Thrombosis research (Thromb Res) Vol. 85 Issue 1 Pg. 45-51 (Jan 01 1997) ISSN: 0049-3848 [Print] United States
• PMID: 8983124 (Publication Type: Journal Article)

Chemical References

• (2S)-2-(4-(((3S)-1-acetimidoyl-3-pyrrolidinyl)oxy)phenyl)-3-(7-amidino-2-naphtyl)propanoic acid
• Anticoagulants
• Factor Xa Inhibitors
• Naphthalenes
• Propionates

Topics

• Animals
• Anticoagulants (administration & dosage)
• Factor Xa Inhibitors
• Humans
• Injections, Intravenous
• Lasers
• Male
• Microcirculation (pathology)
• Naphthalenes (administration & dosage)
• Propionates (administration & dosage)
• Rats
• Rats, Wistar
• Thrombosis (drug therapy, pathology)