Document Detail


Effects of DX-9065a, an inhibitor of factor Xa, on ellagic acid-induced plantar skin thrombosis assessed in tetrodotoxin- and N(omega)-nitro-L-arginine-treated rats.
MedLine Citation:
PMID:  12719661     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Effects of DX-9065a ((+)-2S-2-[4-[[(3S)-1-acetimidoyl-3-pyrrolidinyl]oxy]phenyl]-3-[7-amidino-2-naphthyl]propanoic acid hydrochloride pentahydrate), a dibasic propanoic acid and an inhibitor of factor Xa, were compared with those of argatroban, a low molecular weight thrombin inhibitor, on the ellagic acid-induced plantar skin thrombosis in the rats treated with tetrodotoxin and N(omega)-nitro-L-arginine. Plantar skin blood flow was measured with laser Doppler flow meters, and skin temperature of the hindlimb was monitored simultaneously. In order to induce thrombus in plantar skin vasculature, ellagic acid (300 microg, i.a.) was injected into a branch of femoral artery. The formation of thrombus in femoral and plantar vessels was assessed by light microscopy. Ellagic acid decreased plantar skin blood flow and skin temperature. Intravenous injections of DX-9065a (3 mg/kg) and argatroban (1-3 mg/kg) significantly inhibited the ellagic acid-induced disturbance of plantar skin blood flow and lowering skin temperature without affecting bleeding time. The oral administration of DX-9065a (30-100 mg/kg) significantly prevented the decrease in skin temperature induced by ellagic acid, but it partially inhibited the disturbance of plantar skin blood flow. DX-9065a and argatroban also prolonged prothrombin time in a dose-dependent manner. These results suggest that DX-9065a effectively prevented thrombosis produced by ellagic acid in the skin circulation without a risk of bleeding.
Authors:
Daisuke Chino; Yukiyoshi Fujita; Kunio Ishii; Koichi Nakayama
Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Journal of pharmacological sciences     Volume:  91     ISSN:  1347-8613     ISO Abbreviation:  J. Pharmacol. Sci.     Publication Date:  2003 Apr 
Date Detail:
Created Date:  2003-04-29     Completed Date:  2004-03-01     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  101167001     Medline TA:  J Pharmacol Sci     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  319-29     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, Faculty of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Dose-Response Relationship, Drug
Ellagic Acid / toxicity*
Factor Xa / antagonists & inhibitors*
Hindlimb / blood supply,  drug effects,  pathology
Male
Naphthalenes / pharmacology,  therapeutic use*
Nitroarginine / pharmacology
Propionic Acids / pharmacology,  therapeutic use*
Rats
Rats, Wistar
Skin / blood supply*,  drug effects,  pathology
Skin Diseases / drug therapy,  pathology,  prevention & control
Tetrodotoxin / pharmacology
Thrombosis / pathology,  prevention & control*
Chemical
Reg. No./Substance:
0/Naphthalenes; 0/Propionic Acids; 155204-81-2/DX 9065a; 2149-70-4/Nitroarginine; 4368-28-9/Tetrodotoxin; 476-66-4/Ellagic Acid; EC 3.4.21.6/Factor Xa

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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