Effect of OKY-1581, a Thromboxane Synthesis Inhibitor, on the Platelet Aggregation and Vasodilation Induced by Injury of Mouse Pial Arterioles

OKY-1581 (sodium [E]-3-[4-(3-pyridylmethyl)-phenyl]-2-methylacrylate) is a known inhibitor of thromboxane synthesis, a class of agents thought potentially useful in treating conditions characterized by platelet aggregation. Doses of 10, 100, and 300 mg/kg were administered intraperitoneally to mice 1 h before their pial vessels were injured by a combination of light from a filtered mercury lamp and intravascular sodium fluorescein. In this model platelet aggregation and arterial dilation are produced. Pretreatment with OKY-1581 had no effect except at the 300-mg/kg dose, which enhanced aggregation as manifested by a decrease in the time required for the noxious stimulus to initiate aggregation. In addition the dilation increased in magnitude as compared with that in controls. The latter result is compatible with a decreased synthesis of thromboxane, a known constrictor of cerebral vessels. However, the enhancement of aggregation by a high dose of OKY-1581 was unexpected and paradoxical. The data do not support the use of thromboxane synthesis inhibitors as therapy for conditions caused by platelet aggregation, but the results may be dependent upon the species, the vascular bed, or the method used to induce aggregation.