The antithrombotic effect of synthetic low molecular weight human factor Xa inhibitor, DX-9065a, on He-Ne laser-induced thrombosis in rat mesenteric microvessels.
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.
Yamashita
T
T
Laboratory of Physiology, Faculty of Nutrition, Kobe Gakuin University, Japan.
Tsuji
T
T
Matsuoka
A
A
Giddings
J C
JC
Yamamoto
J
J
D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage*; D065427:Factor Xa Inhibitors; D006801:Humans; D007275:Injections, Intravenous; D007834:Lasers; D008297:Male; D008833:Microcirculation / Q000473:pathology*; D009281:Naphthalenes / Q000008:administration & dosage*; D011422:Propionates / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D013927:Thrombosis / Q000188:drug therapy* / Q000473:pathology
C086910:(2S)-2-(4-(((3S)-1-acetimidoyl-3-pyrrolidinyl)oxy)phenyl)-3-(7-amidino-2-naphtyl)propanoic acid; D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D009281:Naphthalenes; D011422:Propionates