1. Newer Antiplatelet Agents Epifibatide Tirofiban Etc. Benedict R. Lucchesi, M.D., Ph.D. Department of Pharmacology University of Michigan Medical School

2. Epifibatide (Integrelin™) Integrelin - a cyclic peptide antagonist, has been administered to humans with positive results. Must be administered by continuous infusion 1.0 to 1.5 mg/kg/min. Short duration of action - recovery of platelet function within 2-4 hours after termination of the infusion.

3. Tirofiban (Aggrastat™) Development based on anti-clotting components in the venom of an African snake, the saw-scaled viper. Antiplatelet function in humans Indicated for use in patients with unstable angina and non-Q-wave myocardial infarction. Used with heparin and aspirin for treatment of acute coronary syndrome. Must be administered by continuous infusion.

4. DMP 728 (DuPont) Cyclic RGD analog that exhibits recognition specificity toward the GPIIb/IIIa receptor. Binds with high affinity (inhibiting adhesive proteins from binding and displacing previously bound fibrinogen from activated platelets). Effective after parenteral and oral administration.

5. DMP728 - a Low Molecular Weight Platelet GPIIb/IIIa Fibrinogen Receptor Antagonist Incorporating the RGD Sequence

6. Other Glycoprotein IIb/IIIa Antagonists in Clinical Trial Lamofiban (Ro44-9883) [Hoffman LaRoche] Non-peptide GPIIb/IIIa receptor antagonist In clinical trial in patients with unstable angina and myocardial infarction and in patients having angioplasty. Other Orally Active GPIIb/IIIa Receptor Inhibitors in Clinical Trial (NAME). Lotrifiban (BRAVO) Lefradifiban (FROST) Orbofiban (OPUS/TIMI-16) Sibrafiban (SYMPHONY)

7. Essential Thrombocythemia Anagrelide (Argylin™) A life-threatening condition characterized by elevated blood platelet counts. This condition results in an abnormally high incidence of adverse events associated with thrombosis (blood clotting), including heart attack and stroke - incidence in U.S. is 7 / 100,000 individuals. ANAGRELEIDE is indicated for the treatment of essential thrombocythemia to reduce elevated platelet counts and the risk of thrombosis. Therapeutic doses do not produce significant changes in white or red cell counts and has not been shown to be leukemogenic. The drug's labeling provides guidelines for treatment of asymptomatic young adults with essential thrombocythemia. The most frequently reported adverse reactions were mild and self- limiting and included headache, palpitations, diarrhea, and abdominal pain.