HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Inhibition of coronary artery reocclusion after thrombolysis with an RGD-containing peptide with no significant effect on bleeding time.

AbstractBACKGROUND:
A synthetic RGD-containing cyclic peptide, TP9201, specific for the platelet alpha IIb beta 3 receptor complex, was tested for its ability to accelerate thrombolysis and prevent reocclusion in experimentally induced coronary artery thrombosis.
METHODS:
Anesthetized, open-chest dogs with occlusive thrombi received tissue plasminogen activator with TP9201 (113 micrograms/kg bolus; 2.7 micrograms/kg/min infusion, n = 7) or saline control (n = 9).
RESULTS:
A 2.8-fold increase in the duration of vessel patency from 52.7 +/- 63.7 min to 149.1 +/- 63.7 min (P < 0.05) was observed with TP9201 treatment. The mean duration of vessel occlusion was reduced 2.4-fold from 172.4 +/- 81.1 min to 71.7 +/- 63.7 min (P < 0.05). Administration of TP9201 reduced the mean time to lysis from 76.6 +/- 42.9 min to 54.4 +/- 42.9 min, but thrombolysis was not significantly accelerated. Persistent patency was observed in four out of seven of the treated dogs compared with none of the nine in the control group (P < 0.05). Administration of TP9201 inhibited ex-vivo platelet aggregation stimulated by ADP (30 microM) or collagen (10 micrograms/ml). No thrombocytopenia or changes in hemodynamic parameters were observed in the treated group compared with the control group. Peptide TP9201 had no effect on bleeding time and the inhibitory effect on ex-vivo platelet aggregation was rapid and reversible. The pharmacodynamic half-life of TP9201 was approximately 1 h with ex-vivo platelet activity returning to baseline within 2 h of discontinuation of treatment.
CONCLUSIONS:
TP9201 may be an effective therapy for the prevention of re-thrombosis after thrombolytic therapy without adversely affecting hemostasis.
AuthorsJ F Tschopp, E M Driscoll, D X Mu, S C Black, M D Pierschbacher, B R Lucchesi
JournalCoronary artery disease (Coron Artery Dis) Vol. 4 Issue 9 Pg. 809-17 (Sep 1993) ISSN: 0954-6928 [Print] England
PMID8287215 (Publication Type: Comparative Study, Journal Article)
Chemical References
  • Peptides, Cyclic
  • Platelet Aggregation Inhibitors
  • Recombinant Proteins
  • TP 9201
  • Tissue Plasminogen Activator
Topics
  • Animals
  • Bleeding Time
  • Coronary Thrombosis (physiopathology, prevention & control)
  • Dogs
  • Dose-Response Relationship, Drug
  • Hemostasis (drug effects)
  • Models, Biological
  • Peptides, Cyclic (pharmacology, therapeutic use)
  • Platelet Aggregation (drug effects)
  • Platelet Aggregation Inhibitors (pharmacology, therapeutic use)
  • Random Allocation
  • Recombinant Proteins
  • Recurrence
  • Thrombolytic Therapy
  • Tissue Plasminogen Activator (pharmacology, therapeutic use)
  • Vascular Patency (drug effects)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: