Diadenosine 5',5'''-P1,P4-tetraphosphate, a potential antithrombotic agent.

Diadenosine tetraphosphate (AP4A), a competitive inhibitor of ADP-induced platelet aggregation, was tested as an antithrombotic agent in a rabbit intracarotid thrombosis model previously shown to be sensitive to antiplatelet agents. Eighty-four percent of control rabbits formed clots. The infusion of AP4A at a dose of 50 mg/kg over 2 hours reduced the incidence of thrombosis to 56% (p less than 0.05). Blood AP4A increased 125-fold at the end of infusion, but was completely cleared within 10 minutes. Plasma ATP showed bimodal early and late increases. Platelets recovered from AP4A-treated rabbits exhibited a pattern of reduced reactivity to ADP, but not to collagen, similar to platelets exposed to AP4A in vitro. This study shows that AP4A may be a potentially useful antithrombotic agent.