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Phase separation in phosphatidylcholine bilayers as a predictor of inhibition of blood platelet aggregation by amantadines
Authors:Robert W Colman  Jaya Kuchibhotla  Mahendra K Jain  Roger K Murray
Institution:1. Coagulation Unit, Hematology-Oncology Section, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pa. 19104, USA;2. Division of Health Sciences, University of Delaware, Newark, Del. 19711, USA;3. Department of Chemistry, University of Delaware, Newark, Del. 19711, U.S.A.
Abstract:The ability of eleven amantadine derivatives to induce phase separation in dipalmitoyl phosphatidylcholine bilayers was studied by differential scanning calorimetry. The relative potency varied with the shape and size of the hydrocarbon cage. These agents also markedly inhibited blood platelet aggregation. The relative potencies of these compounds to induce phase separation showed a significant correlation (r = 0.70) with their platelet inhibitory activity suggesting that their pharmacologic action may be at the level of the platelet membrane. The effective concentration of the parent component amantadine is similar to its pharmacologic concentration suggesting its use as an anti-platelet drug.
Keywords:HHW′  half-height width  concentration of the amantadine derivative that inhibits platelet aggregation by 50%
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