Effect of eicosatetraenyl (3-aminopropyl) phosphonate (URI-73A) on platelet aggregation and arachidonic acid metabolism.

Eicosatetraenyl (3-aminopropyl) phosphonate (URI-73A), an experimental anti-hypertensive drug, when tested in vitro, inhibits platelet aggregation especially that induced by arachidonic acid (AA) and to a lesser degree by epinephrine. Preincubation of human platelets with this compound in the majority of individuals resulted in a dose-dependent inhibition of the platelet response to AA, mostly in the form of a delay and a reduction of maximal aggregation. Platelets from two smaller groups of donors either exhibited full aggregation or no aggregation. Both the prelabel and pulse label techniques used to study arachidonic acid metabolism yielded complementary results. Production of thromboxane and hydroxy fatty acids was reduced in thrombin-aggregated washed platelets preincubated with URI-73A. In addition, the release of AA from phospholipids was inhibited. Its complex effects on human platelets suggest that URI-73A may, as an AA analog, depress cyclooxygenase and lipoxygenase, and as a phospholipid analog inhibit phospholipase activity.