A new thromboxane receptor antagonist, Z-335, ameliorates experimental thrombosis without prolonging the rat tail bleeding time.

Abstract

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.

• Authors: T Tanaka, S Ito, R Higashino, Y Fukuta, Y Fukuda, M Takei, T Kurimoto, H Tamaki
• Journal: Thrombosis research (Thromb Res) Vol. 91 Issue 5 Pg. 229-35 (Sep 01 1998) ISSN: 0049-3848 [Print] United States
• PMID: 9755835 (Publication Type: Journal Article)

Chemical References

• Fibrinolytic Agents
• Indans
• Receptors, Thromboxane
• Z 335
• Thromboxane A2

Topics

• Animals
• Bleeding Time
• Fibrinolytic Agents (therapeutic use)
• Indans (therapeutic use)
• Male
• Mice
• Mice, Inbred ICR
• Rats
• Rats, Sprague-Dawley
• Receptors, Thromboxane (antagonists & inhibitors, physiology)
• Thrombosis (drug therapy, physiopathology)
• Thromboxane A2 (physiology)