Antithrombotic effect of a humanized anti-GPIIb/IIIa monoclonal antibody, YM207, in a photochemically induced thrombosis model in monkeys

Eur J Pharmacol. 1995 Jun 12;279(2-3):115-21. doi: 10.1016/0014-2999(95)00136-9.

Abstract

We investigated the antithrombotic effects of a F(ab')2 fragment of a humanized anti-platelet glycoprotein (GP) IIb/IIIa monoclonal antibody, YM207, in a platelet-rich thrombosis model. Thrombus was induced in a mesenteric venule of squirrel monkeys by irradiation with filtered light in combination with i.v. administration of a fluorescent dye (sodium fluorescein). Time to occlusive thrombus formation was significantly prolonged by i.v. bolus injection of 0.3 mg/kg of YM207. At doses of 1 mg/kg and 3 mg/kg, complete occlusion did not occur during 60 min of the observation. Platelet aggregation in platelet-rich plasma was inhibited by YM207 at doses 0.3 mg/kg or more. A good correlation was obtained between inhibition of platelet aggregation and the percentage of GPIIb/IIIa receptors blocked by YM207. Bleeding time was significantly prolonged at a dose of 3 mg/kg. Platelet counts showed no significant change. These results suggest that YM207 is effective in preventing platelet-rich thrombus formation without inducing the prolongation of bleeding time or a significant decrease in platelet count. YM207 may be a useful therapeutic agent for the treatment of thrombotic disorders.

MeSH terms

  • Adenosine Diphosphate / pharmacology
  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • Binding Sites, Antibody / drug effects
  • Blood Coagulation / drug effects
  • Enzyme-Linked Immunosorbent Assay
  • Fibrinolytic Agents / pharmacology*
  • Humans
  • In Vitro Techniques
  • Photochemistry
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / pharmacology
  • Platelet Glycoprotein GPIIb-IIIa Complex / immunology*
  • Saimiri
  • Thrombosis / chemically induced
  • Thrombosis / prevention & control*

Substances

  • Antibodies, Monoclonal
  • Fibrinolytic Agents
  • Platelet Aggregation Inhibitors
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Adenosine Diphosphate