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Diadenosine 5',5'''-P1,P4-tetraphosphate, a potential antithrombotic agent
1Department of Biomedical Research, St. Elizabeth's Hospital, Tufts University School of Medicine, Boston, MA.
Thrombosis Research
|March 15, 1988
Summary
Diadenosine tetraphosphate (AP4A) shows potential as an antithrombotic agent. In a rabbit model, AP4A significantly reduced clot formation, indicating its efficacy in preventing thrombosis.
Area of Science:
- Biochemistry
- Pharmacology
- Hematology
Background:
- Diadenosine tetraphosphate (AP4A) is known to inhibit adenosine diphosphate (ADP)-induced platelet aggregation.
- Platelet aggregation plays a critical role in thrombosis.
Purpose of the Study:
- To evaluate the antithrombotic potential of AP4A.
- To assess AP4A's efficacy in a rabbit intracarotid thrombosis model.
Main Methods:
- Utilized a rabbit intracarotid thrombosis model sensitive to antiplatelet agents.
- Administered AP4A intravenously over 2 hours at a dose of 50 mg/kg.
- Measured thrombosis incidence, blood AP4A levels, plasma adenosine triphosphate (ATP), and platelet reactivity to ADP and collagen.
Main Results:
- Control rabbits had an 84% thrombosis incidence.
- AP4A infusion reduced thrombosis incidence to 56% (p < 0.05).
- Blood AP4A levels increased 125-fold during infusion but were cleared within 10 minutes. Platelets from treated rabbits showed reduced reactivity to ADP but not collagen.
Conclusions:
- AP4A demonstrates antithrombotic properties in vivo.
- AP4A may be a promising therapeutic agent for preventing thrombosis.