Z-335, a new thromboxane A(2) receptor antagonist, prevents arterial thrombosis induced by ferric chloride in rats.

Abstract

We examined the antithrombotic effect of Z-335 ((+/-)-sodium [2-(4-chlorophenylsulfonylaminomethyl)indan-5-yl]acetate monohydrate), an orally active thromboxane A(2) receptor (TP-receptor) antagonist that ameliorates experimental gangrene, using a rat arterial thrombosis model. The thrombi were induced by topical application of 50% ferric chloride solution to the rats abdominal artery. Z-335 (0.3-3 mg/kg, p.o.) inhibited thrombus formation in a dose-dependent manner. The antithrombotic effect of Z-335 (1 and 3 mg/kg, p.o.) was almost equivalent with that of cilostazol (100 mg/kg, p.o.), a selective phosphodiesterase type III inhibitor. The effect of Z-335 (3 mg/kg, p.o.), but not cilostazol, persisted for 16 h. Z-335, but not cilostazol, inhibited platelet aggregation induced by U-46619 (a TP-receptor agonist, 9, 11-dideoxy-9alpha,11alpha-methanoepoxy prostaglandin F(2alpha)) for 16 h in rat whole blood. Histopathological examination also revealed that Z-335 prevented ferric chloride-induced thrombus formation. These results suggest that Z-335 may prevent ferric chloride-induced arterial thrombosis through its antiplatelet action by blocking TP-receptor activation.

• Authors: T Tanaka, R Sato, T Kurimoto
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 401 Issue 3 Pg. 413-8 (Aug 11 2000) ISSN: 0014-2999 [Print] Netherlands
• PMID: 10936501 (Publication Type: Journal Article)

Chemical References

• Chlorides
• Ferric Compounds
• Fibrinolytic Agents
• Indans
• Platelet Aggregation Inhibitors
• Receptors, Thromboxane
• Tetrazoles
• Z 335
• Cilostazol
• ferric chloride

Topics

• Administration, Oral
• Animals
• Aorta, Abdominal (drug effects, pathology)
• Chlorides
• Cilostazol
• Dose-Response Relationship, Drug
• Ferric Compounds (adverse effects)
• Fibrinolytic Agents (pharmacology)
• Indans (pharmacology)
• Male
• Platelet Aggregation (drug effects)
• Platelet Aggregation Inhibitors (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Receptors, Thromboxane (antagonists & inhibitors)
• Tetrazoles (pharmacology)
• Thrombosis (chemically induced, prevention & control)
• Time Factors