Effect of a novel thromboxane (TX) A_2 receptor antagonist, S-145, on arachidonate-induced cerebral infarction in rabbits and sudden death in mice

• Published in: Japanese Journal of Pharmacology 1988, Vol.46 (suppl), p.280-280
• Main Authors: Hirokuni Jyoyama, Atsushi Kurosawa
• Format: Article
• Language: Japanese
• ISSN: 0021-5198

A newly synthesized thromboxane A_2 receptor antagonist, (±)-5(Z)-(3-endo-phenyl-sulfonylamido「2.2.1.」bicyclohept-exo-2-yl)heptanoic acid (S-145) was examined for its preventive effect on arachidonate (AA)-induced cerebral infarction and sudden death (acute pulmonary thromboembolic death) in animals. The cerebral infarction model was made by continuous infusion of AA (1 mg/animal/min for 30 min) into the left internal carotid artery of the rabbit (Japan. J. Pharmacol., 41, p393, 1986). Definite prevention of the cerebral infarction was observed by dosing 0.1 mg/kg i.v. or 1 mg/kg p,o, of S-145 before the AA infusion. The analogous prevention was obtained by dosing 3 mg/kg p,o, of ON0-3708 or 10 mg/kg p.o. of dazoxiben. The sudden death was produced by an i,v, injection of AA to mice at a dose of 100 mg/kg. S-145 caused a strong prevention of the AA-induced sudden death (ED50：0.1 mg/kg i.v. and 2 mg/kg p.o.). The duration of action of S-145 was over 4 hr at a dose of 10 mg/kg p.o. Thvs, S-145 is likely to be useful as an anti-thrombotic agent.