title: Anticoagulant, anti-aggregation and antithrombotic effects of a novel hexapeptide.
abstract: OBJECTIVE
  Hexapeptide is a novel synthetic oligopeptide with a structure similar to that of eptifibatide. This study was designed to investigate the anticoagulant, anti-aggregation, disaggregation and anti-thrombogenesis effects of hexapeptide.
  
  
  METHODS
  The effects of antiplatelet aggregation induced by adenosine diphosphate (ADP), arachidonic acid (AA) and thrombin, and the effect of disaggregation of platelet aggregation induced by ADP were determined. The anticoagulation indexes were determined by different kits.
  
  
  RESULTS
  Hexapeptide 1 × 10(-5) -1 × 10(-4) m could significantly prolong rabbit blood clotting time, thrombin time, prothrombin time and activated partial thromboplastin enzyme time, and reduce the length, wet weight, dry weight and the index of thrombus in a concentration-dependent manner. Hexapeptide 1 × 10(-4) m decreased platelet adhesion rate by 40.2%. The platelet aggregation inhibition of hexapeptide in dogs and humans was more obvious than in rabbits and rats. The aggregation inhibition rate of 1 × 10(-5) m hexapeptide in dogs, rabbits, rats and humans induced by ADP was 93.9 ± 1.3%, 66.2 ± 1.4%, 76.1 ± 3.2% and 99.8 ± 0.2%, respectively; the 50% inhibitory concentration (IC50) of hexapeptide was 7.24 × 10(-8), 3.24 × 10(-6), 6.61 × 10(-6) and 8.91 × 10(-8) m, respectively. For the aggregation inhibition rate of hexapeptide in dogs, rabbits and humans induced by AA, the IC50 was 1.29 × 10(-9), 1.32 × 10(-6) and 9.33 × 10(-8) m, respectively; the IC50 of aggregation inhibition rates induced by thrombin was 2.88 × 10(-6), >1 × 10(-5) and 4.17 × 10(-6) m, respectively. The disaggregation rate of 1 × 10(-4) m hexapeptide in dog induced by ADP was 68.8 ± 7.4%.
  
  
  CONCLUSIONS
  Hexapeptide has anticoagulant, antiplatelet aggregation, disaggregation and antithrombotic effects in vitro.
authors: Department of Pharmacy, Affiliated Hospital of Xi'an Medical College, China.
authors: Li-hui
authors: LH
authors: Long
authors: Yong-xiao
authors: YX
authors: Cao
authors: Zhao
authors: Z
authors: Ma
authors: Jing
authors: J
authors: Liu
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects*; D004285:Dogs; D000077542:Eptifibatide; D006801:Humans; D009842:Oligopeptides / Q000494:pharmacology*; D010314:Partial Thromboplastin Time; D010455:Peptides / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011517:Prothrombin Time; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013918:Thrombin Time
chemical_list: D000925:Anticoagulants; D009842:Oligopeptides; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D000077542:Eptifibatide