Drug-Membrane Interactions -- Contents -- Preface -- Foreword -- Introduction -- 1 Function, Composition, and Organization of Membranes -- 1.1 The Physiology of Cells and the Importance of Membranes for their Function -- 1.2 Composition and Organization of Membranes -- 1.2.1 Mammalian Membranes -- 1.2.2 Bacterial Membranes -- 1.2.3 Fungal Membranes -- 1.2.4 Artificial Membranes, Liposome Preparation, and Properties -- 1.3 Dynamic Molecular Organization of Membranes -- 1.3.1 Thermotropic and Lysotropic Mesomorphism of Phospholipids -- 1.3.2 Phase Separation and Domain Formation -- 1.4 Possible Effects of Drugs on Membranes and Effects of Membranes on Drug Molecules -- References -- 2 Octanol-Water Partitioning versus Partitioning into Membranes -- References -- 3 Analytical Tools for the Analysis and Quantification of Drug-Membrane Interactions -- 3.1 High-performance Liquid Chromatography (HPLC) -- 3.1.1 Determination of the Retention Time on "Artificial Membrane" Columns -- 3.2 Displacement of (45)Ca(2+) from Phospholipid Head Groups -- 3.2.1 Studies of Drug-Membrane Interactions using Phospholipid Monolayers -- 3.3 Differential Scanning Calorimetry (DSC) -- 3.3.1 Phase Transition and Domain Formation -- 3.4 Fluorescence Techniques -- 3.5 Fourier Transform Infrared Spectroscopy (FT-IR) -- 3.6 Electron Spin Resonance (ESR) -- 3.7 Small-angle Neutron and X-ray Diffraction -- 3.8 Nuclear Magnetic Resonance (NMR) -- 3.8.1 Study of Membrane Polymorphism by (31)P-NMR -- 3.8.2 Effect of Cholesterol and Diacylglycerols -- 3.8.3 Effect of Drugs -- 3.8.3.1 (31)P-NMR for the Study of Changes in Orientation of Phospholipid Head Group -- 3.8.4 Determination of Drug Transmembrane Transport -- 3.8.5 (1)H-NMR in Combination with Pr(3+) for the Study of Drug Location.

3.8.6 The Use of (2)H-NMR and (13)C-NMR to Determine the Degree of Order and the Molecular Dynamics of Membranes -- 3.8.7 Change in relaxation rate, 1/T2: a Method of Quantifying Drug-Membrane Interaction -- 3.8.8 NOE-NMR in the Study of Membrane-induced Changes in Drug Conformation -- 3.9 Circular Dichroism (CD) -- 3.10 UV Spectroscopy -- 3.11 Combined Techniques for Studying Drug-Membrane Interaction -- 3.11.1 Combination of DSC and NMR -- 3.11.2 Combination of DSC and X-ray Diffraction -- 3.11.3 Combination of DSC and ESR -- 3.11.4 Combination of DSC and Fluorescence -- 3.11.5 Combination of FT-IR and NMR -- 3.11.6 Combination of UV and (2)H-NMR -- 3.11.7 Combination of DSC, FT-IR, and NMR -- 3.12 Summary -- References -- 4 Drug-Membrane Interaction and Pharmacokinetics of Drugs -- 4.1 Drug Transport -- 4.1.1 Absorption Models -- 4.1.1.1 Caco-2 Cells as an Absorption Model -- 4.1.1.2 Parallel Artificial Membrane Permeation Assay (PAMPA) -- 4.1.1.3 Surface Plasmon Resonance Biosensor Technique -- 4.1.1.4 The Use of IAM Columns -- 4.1.1.5 Partitioning into Immobilized Liposomes -- 4.1.2 Computational Methods, QSAR -- 4.2 Drug Distribution -- 4.2.1 Distribution into the Brain Compartment -- 4.2.2 Distribution, Localization, and Orientation of Drugs in Various Tissues and Membranes -- 4.2.3 Distribution in vivo -- 4.3 Uptake into and Distribution within Bacterial Cells -- 4.3.1 Diffusion Through the Outer Asymmetric Core of E. coli -- 4.3.2 Self-promoted Uptake of Antibacterial Peptides -- 4.4 Drug Accumulation, Toxicity, and Selectivity -- 4.4.1 Selectivity -- References -- 5 Drug-Membrane Interactions and Pharmacodynamics -- 5.1 Drug Efficacy -- 5.1.1 Effect on Membrane-integrated Enzymes -- 5.1.1.1 Activation and Inhibition of Protein Kinase C (PKC) -- 5.1.1.2 Inhibition of Phospholipase A2 (PLA2).

5.1.1.3 Drug-Membrane Interactions and Inhibition of Na(+),K(+)-ATPase -- 5.1.2 Release of Pharmacological Response -- 5.1.2.1 Effect of Anesthetics -- 5.1.2.2 Negative Chronotropic (Cardiodepressant) Effect -- 5.1.2.3 Anti-inflammatory Effect -- 5.1.2.4 Effect of Antiarrhythmics -- 5.1.2.5 Calcium-Channel Blocking Activity -- 5.1.2.6 α-Adrenoceptor Agonist Activity -- 5.1.2.7 Anticonvulsive Effect -- 5.1.2.8 Antioxidant Effect -- 5.1.2.9 Antineoplastic Activity of Ether Phospholipids -- 5.1.2.10 Antimalarial Activity of Chloroquine -- 5.1.2.11 Conformation of Acetogenin Derivatives in Membranes and the Relation to Cytotoxicity -- 5.1.2.12 A Membrane-forming and Inflammation-inducing Bacterial Macromolecule -- 5.1.2.13 Drug-Membrane Interactions involved in Alzheimer's Disease -- 5.2 Drug Resistance -- 5.2.1 Bacterial Cells -- 5.2.2 Reversal of Multidrug Resistance in Tumor Cells -- 5.2.3 Proposed Mechanisms of Action -- 5.2.4 Change in Composition of Membranes and Influence on P-gp, Cytotoxic Agents, and MDR-reversing Drugs -- 5.2.4.1 Comparison of Lipid Composition of Sensitive and Resistant Cells -- 5.2.4.2 Membrane Composition and Functioning of Membrane-embedded Proteins -- 5.2.5 Membrane Composition, Drug Binding, and Transport Kinetics -- 5.2.6 SARs and QSARs for Cytotoxic Agents and MDR Modifiers -- References -- 6 Computer Simulation of Phospholipids and Drug-Phospholipid Interactions -- 6.1 Modeling Strategies for Studying Phospholipids and Drug-Phospholipid Interactions -- 6.1.1 Types of Representation of the Simulated System -- 6.1.1.1 Mean Field Simulations -- 6.1.1.2 All-atom Simulations -- 6.1.2 Monte Carlo Simulations -- 6.1.3 Molecular Dynamics Simulations -- 6.1.3.1 Starting Structure, and Equilibrium Time -- 6.1.3.2 Boundary Conditions -- 6.1.3.3 Long-range Electrostatics and Non-bonded Cut-off -- 6.1.3.4 Kind of Simulation System.

6.2 Computer Simulations with Phospholipids -- 6.2.1 Distribution of Solutes -- 6.2.2 Mechanism of Diffusion through Phospholipid Membranes -- 6.2.3 Small Molecules and their Interaction with Phospholipids -- 6.2.3.1 Anesthetics -- 6.2.3.2 Dihydropyridines -- 6.2.4 Effect of Cholesterol on Membrane Structure -- 6.2.5 Interactions of peptides with phospholipids -- 6.2.5.1 Mean Field Simulations -- 6.2.5.2 All-atom Simulations -- 6.2.6 Simulations of Pore-forming Peptides and of the Diffusion of Ions through Ion Channels -- 6.2.7 Non-equilibrium Molecular Dynamics Simulations -- 6.3 Concluding Remarks -- References -- Index.