The displacement of phenothiazines from phospholipid binding sites by cholesterol

The interaction of the phenothiazine type drug, methochlorpromazine, with phosphatidylcholine membranes has been investigated by using this tranquilizer in a deuterium labeled form. Two distinct binding sites were found, with exchange between them being fast on the 2H NMR time scale. Cholesterol preferentially displaces the chlorpromazine from the more hydrophobic of these sites, making possible an explanation of the modulation of the effects of amphipathic agents by cholesterol. In addition, the phenomenon of displacement of membrane active agents by sterols may explain discrepancies between membrane/water partition coefficients as measured by centrifugation and hygroscopic desorption.