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.
Louie
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Department of Biomedical Research, St. Elizabeth's Hospital, Tufts University School of Medicine, Boston, MA.
Kim
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BK
Zamecnik
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D000227:Adenine Nucleotides / Q000097:blood / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000097:blood*; D000818:Animals; D015226:Dinucleoside Phosphates; D004305:Dose-Response Relationship, Drug; D005343:Fibrinolytic Agents; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011817:Rabbits
D000227:Adenine Nucleotides; D015226:Dinucleoside Phosphates; D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; C020733:diadenosine tetraphosphate; D000255:Adenosine Triphosphate