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 A2 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.
Tanaka
T
T
Central Research Laboratories, Zeria Pharmaceutical Co. Ltd., Saitama, Japan.
Ito
S
S
Higashino
R
R
Fukuta
Y
Y
Fukuda
Y
Y
Takei
M
M
Kurimoto
T
T
Tamaki
H
H
D000818:Animals; D001760:Bleeding Time; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D007189:Indans / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D051381:Rats; D017207:Rats, Sprague-Dawley; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors* / Q000502:physiology; D013927:Thrombosis / Q000188:drug therapy* / Q000503:physiopathology; D013928:Thromboxane A2 / Q000502:physiology
D005343:Fibrinolytic Agents; D007189:Indans; D017482:Receptors, Thromboxane; C115527:Z 335; D013928:Thromboxane A2