A New Thromboxane Receptor Antagonist, Z-335, Ameliorates Experimental Thrombosis without Prolonging the Rat Tail Bleeding Time

We investigated the antithrombotic activity of Z-335, a new thromboxane A 2 receptor antagonist, using experimental thrombosis models, and also tested its effect on the rat tail bleeding time. Z-335 (0.1, 0.3, and 1 mg/kg, p.o.) dose-dependently prevented the occurrence of arachidonic acid-induced p...

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Bibliographic Details
Published in:Thrombosis research 1998-09, Vol.91 (5), p.229-235
Main Authors: Tanaka, Takao, Ito, Shigeru, Higashino, Raita, Fukuta, Yoshihisa, Fukuda, Youichi, Takei, Mineo, Kurimoto, Tadashi, Tamaki, Hajime
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Bleeding Time
Blood. Blood coagulation. Reticuloendothelial system
Fibrinolytic Agents - therapeutic use
Hind limb injury
Indans - therapeutic use
Male
Medical sciences
Mice
Mice, Inbred ICR
Pharmacology. Drug treatments
Photochemically induced thrombosis
Pulmonary thromboembolism
Rats
Rats, Sprague-Dawley
Receptors, Thromboxane - antagonists & inhibitors
Receptors, Thromboxane - physiology
Thrombosis - drug therapy
Thrombosis - physiopathology
Thromboxane A2 - physiology
thromboxane receptor antagonist
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Summary:We investigated the antithrombotic activity of Z-335, a new thromboxane A 2 receptor antagonist, using experimental thrombosis models, and also tested its effect on the rat tail bleeding time. Z-335 (0.1, 0.3, and 1 mg/kg, p.o.) dose-dependently prevented the occurrence of arachidonic acid-induced pulmonary thromboembolism in mice. During photochemically induced thrombosis in the femoral artery of guinea pigs, Z-335 (0.3, 1, and 3 mg/kg, i.v.) dose-dependently prolonged the time required to form thrombi. Moreover, Z-335 (10 mg/kg/day, p.o.) strongly suppressed lauric acid-induced hind limb injury in rats. Z-335 (0.3, 3, 30, and 300 mg/kg, p.o.) did not prolong the tail bleeding time in rats. These results strongly suggest that Z-335 ameliorates experimental thrombosis without prolonging the rat tail bleeding time, and may therefore be a useful antithrombotic drug.
ISSN:0049-3848
1879-2472
DOI:10.1016/S0049-3848(98)00103-0