PMID- 11057859
OWN - NLM
STAT- MEDLINE
DCOM- 20010222
LR  - 20141120
IS  - 0340-6245 (Print)
IS  - 0340-6245 (Linking)
VI  - 84
IP  - 4
DP  - 2000 Oct
TI  - Pre-clinical pharmacological profile of the novel glycoconjugate Org 36764 with 
      both factor Xa and thrombin (IIa) inhibitory activities.
PG  - 611-20
AB  - Org 36764, is an antithrombin III (AT) and thrombin binding carbohydrate, which 
      accelerates the inactivation of both factor Xa and thrombin by AT. It displays in 
      buffer an anti-Xa and anti-thrombin activity of 415 and 2 U/mg, respectively, 
      compared to 172 and 114 U/mg, respectively, for unfractionated heparin (UFH), Org 
      36764 does not cross-react with HIT (heparin induced thrombocytopenia) antibodies 
      and is not neutralised by PF4. In experimental models in rats, on a molar basis. 
      Org 36764 was more active than the pentasaccharide SanOrg 34006 (= AT binding 
      domain of Org 36764) in arterial thrombosis, but both were equally active in 
      venous thrombosis. In arterial thrombosis following endothelial damage by ferric 
      chloride, Org 36764 was more active than the LMW heparin enoxaparin and SanOrg 
      34006 and similar active to UFH. At AT saturating doses the bleeding enhancement 
      was not more than 3.5 times the control value. Org 36764 was more active in 
      suppressing in vivo thrombus formation on stents than UFH. SanOrg 34006 or a 
      combination of ticlopidine and aspirin. The results indicate that the novel drug 
      Org 36764 is a drug with antithrombotic potential against venous and arterial 
      thrombosis.
FAU - Vogel, G M
AU  - Vogel GM
AD  - Department of Pharmcology, Scientific Development Group N.V. Organon, Oss, The 
      Netherlands. g.vogel@organon.oss.akzonobel.nl
FAU - van Amsterdam, R G
AU  - van Amsterdam RG
FAU - van Dinther, T G
AU  - van Dinther TG
FAU - Tromp, M
AU  - Tromp M
FAU - Meuleman, D G
AU  - Meuleman DG
LA  - eng
PT  - Journal Article
PL  - Germany
TA  - Thromb Haemost
JT  - Thrombosis and haemostasis
JID - 7608063
RN  - 0 (Anticoagulants)
RN  - 0 (Carbohydrates)
RN  - 0 (Factor Xa Inhibitors)
RN  - 0 (Glycoconjugates)
RN  - 0 (Org 36764)
RN  - 9000-94-6 (Antithrombin III)
RN  - EC 3.4.21.5 (Thrombin)
SB  - IM
MH  - Animals
MH  - Anticoagulants/*pharmacology/therapeutic use
MH  - Antithrombin III/*pharmacology/therapeutic use
MH  - Carbohydrates/pharmacology
MH  - *Factor Xa Inhibitors
MH  - Glycoconjugates/*pharmacology/therapeutic use
MH  - Male
MH  - Rats
MH  - Rats, Wistar
MH  - Thrombin/*antagonists & inhibitors
MH  - Thrombosis/*drug therapy
EDAT- 2000/11/01 11:00
MHDA- 2001/03/03 10:01
CRDT- 2000/11/01 11:00
PHST- 2000/11/01 11:00 [pubmed]
PHST- 2001/03/03 10:01 [medline]
PHST- 2000/11/01 11:00 [entrez]
AID - 00100611 [pii]
PST - ppublish
SO  - Thromb Haemost. 2000 Oct;84(4):611-20.