Effects of TAK-029, a novel GPIIb/IIIa antagonist, on arterial thrombosis in guinea pigs, dogs and monkeys.

Abstract

The antithrombotic and bleeding time (BT) prolonging effects of TAK-029, a novel GPIIb/IIIa antagonist, were examined in three arterial thrombosis models. In guinea pigs, TAK-029 at 30 micrograms/kg (i.v.) inhibited ADP-induced ex vivo platelet aggregation completely and prolonged BT to 4.5 times the control value 5 min after administration, and it prevented thrombotic occlusion in 2 out of 5 animals in a photochemically-induced basilar thrombosis model. TAK-029 at 100 micrograms/kg (i.v.) prolonged BT more than 9 times 5 min after administration, and it prevented thrombus formation for over 60 min. In dogs, TAK-029 at 30 micrograms/kg (i.v.) inhibited ADP-induced ex vivo platelet aggregation by 87% 5 min after administration, and it prevented thrombotic occlusion in injured and stenosed coronary arteries for 22 min without prolonging the BT. TAK-029 at 100 micrograms/ kg (i.v.) inhibited platelet aggregation completely and prolonged BT 3.6 times 5 min after administration, and it prevented thrombus formation for over 45 min. In monkeys, TAK-029 at 10 micrograms/kg (i.v.) inhibited ADP-induced ex vivo platelet aggregation by 84% and prolonged BT 4.6 times 5 min after the administration, and it prevented thrombotic occlusion in injured and stenosed carotid arteries for 24 min. TAK-029 at 30 micrograms/kg (i.v.) completely inhibited platelet aggregation and thrombus formation for over 60 min, and it prolonged BT more than 7.3 times 60 min after administration. In conclusion, TAK-029 exerted potent antithrombotic effects with BT prolongation in three different arterial thrombosis models. TAK-029 may be effective for the treatment of various arterial thrombotic diseases.

• Authors: M Kawamura, N Tsuji, N Moriya, Z Terashita
• Journal: Thrombosis research (Thromb Res) Vol. 86 Issue 4 Pg. 275-85 (May 15 1997) ISSN: 0049-3848 [Print] United States
• PMID: 9187016 (Publication Type: Journal Article)

Chemical References

• Guanidines
• Platelet Glycoprotein GPIIb-IIIa Complex
• Pyrazines
• TAK 029

Topics

• Animals
• Basilar Artery (drug effects, pathology)
• Bleeding Time
• Carotid Artery Thrombosis (drug therapy, pathology)
• Coronary Thrombosis (drug therapy, pathology)
• Disease Models, Animal
• Dogs
• Female
• Guanidines (administration & dosage, blood, pharmacology)
• Guinea Pigs
• Injections, Intravenous
• Macaca fascicularis
• Male
• Platelet Aggregation (drug effects)
• Platelet Glycoprotein GPIIb-IIIa Complex (antagonists & inhibitors, drug effects)
• Pyrazines (administration & dosage, blood, pharmacology)
• Thrombosis (drug therapy, pathology)