Titre du document / Document title

Z-335, a new thromboxane A₂ receptor antagonist, prevents arterial thrombosis induced by ferric chloride in rats

Auteur(s) / Author(s)

TANAKA T. ⁽¹⁾ ; SATO R. ⁽¹⁾ ; KURIMOTO T. ⁽¹⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Central Research Laboratories, ZERIA Pharmaceutical Co. Ltd., 2512-1 Oshikiri, Kohnan-machi, Ohsato-gun, Saitama, 360-0111, JAPON

Résumé / Abstract

We examined the antithrombotic effect of Z-335 ((±)-sodium [2-(4-chlorophenylsulfonylaminomethyl)indan-5-yl]acetate monohydrate), an orally active thromboxane A₂ 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-9α, 11α-methanoepoxy prostaglandin F_2α) 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.

Revue / Journal Title

European journal of pharmacology   ISSN 0014-2999   CODEN EJPHAZ 

Source / Source

2000, vol. 401, n^o3, pp. 413-418 (13 ref.)

Langue / Language

Anglais

Editeur / Publisher

Elsevier, Amsterdam, PAYS-BAS  (1967) (Revue)

Mots-clés anglais / English Keywords

Thromboxane A2 ; Biological receptor ; Antagonist ; Thrombosis ; Artery ; Antiplatelet agent ; Biological activity ; Animal ; Rat ; Oral administration ; Comparative study ; Cilostazol ; Mechanism of action ; Rodentia ; Mammalia ; Vertebrata ; Arachidonic acid derivatives ; Cardiovascular disease ; Vascular disease ; Arterial disease ;

Mots-clés français / French Keywords

Thromboxane A2 ; Récepteur biologique ; Antagoniste ; Thrombose ; Artère ; Inhibiteur thromboagrégation ; Activité biologique ; Animal ; Rat ; Voie orale ; Etude comparative ; Cilostazol ; Mécanisme action ; Z 335 ; Rodentia ; Mammalia ; Vertebrata ; Arachidonique acide dérivé ; Appareil circulatoire pathologie ; Vaisseau sanguin pathologie ; Artère pathologie ;

Mots-clés espagnols / Spanish Keywords

Tromboxano A2 ; Receptor biológico ; Antagonista ; Trombosis ; Arteria ; Inhibidor tromboagregación ; Actividad biológica ; Animal ; Rata ; Vía oral ; Estudio comparativo ; Cilostazol ; Mecanismo acción ; Rodentia ; Mammalia ; Vertebrata ; Araquidónico ácido derivado ; Aparato circulatorio patología ; Vaso sanguíneo patología ; Arteria patología ;

Localisation / Location

INIST-CNRS, Cote INIST : 13322, 35400009083156.0180