Abstract
The interaction of chlorpromazine (CPZ) with artificial membranes (egg-yolk phosphatidylcholine liposomes) has been studied. Measurements of the surface electric potential, which is modified in the presence of the ionized form of the drug, were obtained by electron paramagnetic resonance spectroscopy (EPR) using a positively charged amphiphilic spin-probe. This probe partitions between the aqueous and lipidic phases depending on the surface potential and on the structural state of the membrane. The surface potential was measured as a function of drug concentration in the range where the spectral line-shapes are not affected by the incorporation of the drug. From these experimental results and through an appropriate formalism we obtain information on the binding of the drug to the lipid bilayer and on the ionization of the drug in the lipidic phase.
Similar content being viewed by others
References
Barthel D, Zschoernig O, Lange K, Lenk R, Arnold K (1988) Interaction of electrically charged drug molecules with phospholipid membranes. Biochim Biophys Acta 945: 361–366
Boggs JM, Yoong T, Hsia JC (1975) Site and mechanism of action: I. Effect of anesthetics and pressure on fluidity of spin-labeled lipid vesicles. Mol Pharmacol 12: 127–135
Cafiso DS, Hubbell WL (1978) Estimation of transmembrane potentials from phase equilibria of hydrophobic paramagnetic ions. Biochemistry 17: 187–195
Cafiso DS, Hubbell WL (1981) EPR determination of membrane potentials. Annu Rev Biophys Bioeng 10: 217–244
Castle JD, Hubbell WL (1976) Estimation of membrane surface potential and charge density from the phase equilibrium of paramagnetic amphiphile. Biochemistry 15: 4818–4831
Eriksson LEG, Westman J (1981) Interaction of some charged amphiphilic drugs with phosphatidylcholine vesicles. A spin label study of surface potential effects. Biophys Chem 13: 253–264
Escudero B, Gutiérrez-Merino C (1987) Effects of local anesthetics on the passive permeability of sarcoplasmic reticulum vesicles to Ca++ and Mg+*. Biochim Biophys Acta 902: 374–384
Fernandez MS (1981) Determination of surface potential in liposomes. Biochim Biophys Acta 646: 27–30
Frezzati WA, Toselli WR, Schreier S (1986) Spin label study of local anesthetic-lipid membrane interactions. Phase separation of the uncharged form and bilayer micellization by the charged form of tetracaine. Biochim Biophys Acta 860: 531–538
Goormaghtigh E, Caspers J, Ruysschaert JM (1981) Lipid-drug electrostatic interactions in model membranes. J Colloid Interface S680: 163–170
Hornby AP, Cullis PR (1981) Influence of local and neutral anaesthetics on the polymorphic phase preferences of eff yolk phosphatidylethanolamine. Biochim Biophys Acta 647: 285–292
Lee AG (1977) Local anesthesia: the interaction between phospholipids and chlorpromazine, propranolol and practolol. Mol Pharmacol 13: 474–487
Lee AG (1978) Effects of charged drugs on the phase transition temperatures of phospholipid bilayers. Biochim Biophys Acta 514: 95–104
Lee AG, East JM, Jones OT, McWhirter J, Rooney EK, Simmonds AC (1983) Binding of dansyl propranolol to the (Ca++ + Mg++)-ATPase. Biochim Biophys Acta 732: 441–454
McIntosh TJ, McDaniel RV, Simon SA (1983) Induction of an interdigitated gel phase in fully hydrated phosphatidylcholine bilayers. Biochim Biophys Acta 731: 109–114
Ohki S (1984) Adsorption of local anesthetics on phospholipid membranes. Biochim Biophys Acta 777: 56–66
Papahadjopoulos D, Jacobson K, Poste G, Shepherd G (1975) Effects of local anesthetics on membrance properties: I. Changes in the fluidity of phospholipid bilayers. Biochim Biophys Acta 394: 504–519
Rooney EK, Lee AG (1983) Binding of hydrophobic drugs to lipid bilayers and to the (Ca++ + Mg++)-ATPase. Biochim Biophys Acta 732: 428–440
Seeman P (1972) The membrane actions of anesthetics and tranquilizers. Pharmacol Rev 24: 583–655
Schwartz MA, McConnell HM (1978) Surface areas of lipid membranes. Biochemistry 17: 837–840
Simmonds AC, East JM, Jones EK, Rooney EK, McWhirter J, Lee AG (1982) Annular and non-annular binding sites on the (Ca++ + Mg++)-ATPase. Biochim Biophys Acta 693: 398–406
Szoka F Jr, Papahadjopoulos D (1980) Comparative properties and preparation of lipid vesicles (liposomes). Annu Rev Biophys Bioeng 9: 467–508
Weld R, Mullikin LJ, Yoshimura T, Helmkamp GM (1984) Partition of amphiphilic molecules into phospholipid vesicles and human erythrocyte ghosts: measurements by ultraviolet difference spectroscopy. Biochemistry 23: 6086–6091
Author information
Authors and Affiliations
Additional information
Correspondence to: C. Anteneodo
Rights and permissions
About this article
Cite this article
Anteneodo, C., Bisch, P.M. & Ferreira Marques, J. Interaction of chlorpromazine with phospholipid membranes. Eur Biophys J 23, 447–452 (1995). https://doi.org/10.1007/BF00196833
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00196833