Richards Quantum Pharmacology

2. Auflage 2013
ISBN: 978-1-4831-6367-3
Verlag: Elsevier Science & Techn.
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, 288 Seiten, Web PDF

Quantum Pharmacology, Second Edition discusses molecular pharmacology, molecular quantum mechanics, and the applications of theory to experiment. The book reviews molecular and quantitative pharmacology, as well as acetylcholines, catecholamines, and histamines. The text also discusses the central nervous system in relation to monoamines, acetylcholines, amino acids, and peptides. The book explains wave functions and orbitals, secular equations, matrix elements, and self-consistent molecular orbitals. One way to improve wave functions as a result of a self-consistent field or as an approximate calculation, is to permit different configurations to interact. Linear mixing will lead to improved wave functions. The investigator can compute wave functions and energies of molecules for any set of nuclear coordinates. Quantum chemical calculations treat conformation as similar with geometry; calculations are performed for a series of positions in one part of a molecule relative to another. The investigator can then compare the energies found in each position. The book points out that calculations of conformational internal energy surfaces for flexible pharmacological molecules treating the molecule or ion as isolated in space fit in with observed results of crystallographic experiments. The text is suitable for pharmacologists, and scientists involved in molecular pharmacology, medicinal chemistry, and quantum chemistry.

Autoren/Hrsg.

Richards, W. G.

Inhaltsverzeichnis

1;Front Cover;1
2;Quantum Pharmacology;2
3;Copyright Page;3
4;Table of Contents;8
5;Preface to second edition;4
6;Preface to first edition;6
7;Introduction;10
8;Part I: Molecular pharmacology;16
8.1;Chapter 1. Small molecules in biology;18
8.1.1;Action Potentials;22
8.1.2;The classification of nerves;23
8.1.3;Neuron structure and junctions;23
8.1.4;Nerve transmitters;26
8.1.5;Synaptic actions of neuro-transmitters;29
8.1.6;Receptors;31
8.1.7;Summary;33
8.1.8;Further reading;33
8.2;Chapter 2. Quantitative pharmacology;34
8.2.1;Pharmacological measurements;34
8.2.2;Responses;35
8.2.3;Dose–response curves;36
8.2.4;Direct binding studies;38
8.2.5;Theories of drug action;40
8.2.6;Quantitative receptor theory;42
8.2.7;Some complications;45
8.2.8;Summary;45
8.2.9;Further reading;46
8.3;Chapter 3. Acetylcholine;47
8.3.1;Voluntary nerves: the neuromuscular junction;48
8.3.2;Autonomie ganglia;53
8.3.3;Post-ganglionic nerve endings;55
8.3.4;Anticholinesterases;57
8.3.5;Acetylcholine release;59
8.3.6;Isolation of acetylcholine receptors;59
8.3.7;Summary;60
8.3.8;Further reading;60
8.4;Chapter 4. Catecholamines;62
8.4.1;The classification of receptors;62
8.4.2;Pharmacological preparations;66
8.4.3;Agonists;66
8.4.4;a-Receptor antagonists;68
8.4.5;ß-Receptor antagonists;70
8.4.6;The ß-adrenergic receptor and adenylate cyclase activity;71
8.4.7;Blockage of release and uptake;72
8.4.8;Monoamine oxidase (MAO) inhibitors;73
8.4.9;Summary;73
8.4.10;Further reading;74
8.5;Chapter 5. Histamine;75
8.5.1;Occurrence;75
8.5.2;Physiological and pathological effects;76
8.5.3;Histamine release;76
8.5.4;Pharmacological testing;77
8.5.5;Agonists;77
8.5.6;H1 Antagonists;79
8.5.7;H2 Antagonists;81
8.5.8;Summary;83
8.5.9;Further reading;83
8.6;Chapter 6. Central nervous system I. Monoamines and acetylcholine;84
8.6.1;Chemical transmitters;85
8.6.2;Catecholamines;86
8.6.3;Histamine;88
8.6.4;Acetylcholine;88
8.6.5;Central nervous system drugs;89
8.6.6;Antipsychotics;90
8.6.7;Antidepressants;91
8.6.8;Psychomotor stimulants;93
8.6.9;Hallucinogens;95
8.6.10;Further reading;96
8.7;Chapter 7. Central nervous system II. Amino acids and

peptides;97
8.7.1;Amino acids;97
8.7.2;Anti-anxiety drugs;100
8.7.3;Anti-epileptic drugs;101
8.7.4;Peptides;101
8.7.5;Analgesics;104
8.7.6;Summary;105
8.7.7;Further reading;105
8.8;Chapter 8. Anaesthetics;106
8.8.1;General anaesthetics;106
8.8.2;Theories of general anaesthesia;108
8.8.3;Local anaesthetics;110
8.8.4;Summary;110
8.8.5;Further reading;111
8.9;Chapter 9. Chemotherapy;113
8.9.1;Sulphonamides;115
8.9.2;Antibiotics;115
8.9.3;Antimalarials;119
8.9.4;Antiviral agents;120
8.9.5;Cancer chemotherapy;121
8.9.6;Summary;122
8.9.7;Further reading;122
8.10;Chapter 10. Other areas;123
8.10.1;Kinins;123
8.10.2;Prostaglandins;124
8.10.3;Anti-inflammatory drugs;124
8.10.4;Hormones;125
8.10.5;Vitamins;128
8.10.6;Summary;129
8.10.7;Further reading;129
9;Part II: Molecular quantum mechanics;130
9.1;Chapter 11. Wave functions and orbitals;132
9.1.1;Wave functions;132
9.1.2;Orbitals;134
9.1.3;Spin-orbitals and antisymmetry;134
9.1.4;Molecular orbitals;137
9.1.5;Secular equations;138
9.1.6;Matrix elements;140
9.1.7;Self-consistent molecular orbitals;141
9.1.8;Configuration interaction;143
9.1.9;Summary;144
9.1.10;Further reading;144
9.2;Chapter 12. Approximate wave functions;145
9.2.1;Ab initio methods;145
9.2.2;Correlation energy;147
9.2.3;Semi-empirical calculations;149
9.2.4;Neglect of differential overlap;150
9.2.5;The use of localized orbitals;151
9.2.6;Use of an undefined hamiltonian operator;151
9.2.7;Computer programs for molecular orbital calculations;152
9.2.8;Summary;152
9.2.9;Further reading;153
9.3;Chapter 13. Calculated molecular properties;155
9.3.1;Energies;155
9.3.2;Molecular geometry;156
9.3.3;Conformation;158
9.3.4;Conformational free energies;160
9.3.5;Ionization potentials and electron affinities;162
9.3.6;Charge distribution;163
9.3.7;Mulliken population analysis;165
9.3.8;Molecular potential fields;166
9.3.9;Frontier electron density;168
9.3.10;Static indices;170
9.3.11;Summary;170
9.3.12;Further reading;171
9.4;Chapter 14. Running a calculation;172
9.4.1;Atomic coordinates;172
9.4.2;Molecular models;173
9.4.3;Atom–atom potential calculations: molecular mechanics;174
9.4.4;Choice of the molecular orbital method;176
9.4.5;Basis sets;177
9.4.6;Configuration interaction;178
9.4.7;Computed properties;179
9.4.8;An example of a calculation: methylamine;179
9.4.9;Computers;181
9.4.10;Summary;183
9.4.11;Further reading;183
10;Part III: Applications of theory to experiment;184
10.1;Chapter 15. Conformations;186
10.1.1;Calculation procedure;187
10.1.2;Notation and presentation of results;188
10.1.3;Results for isolated molecular species;188
10.1.4;Acetylcholine;190
10.1.5;Catecholamines;192
10.1.6;Histamine;192
10.1.7;5-Hydroxytryptamine;192
10.1.8;Limitations of isolated molecule calculations;193
10.1.9;The Venn diagram approach;193
10.1.10;The use of computer graphics;200
10.1.11;Series with several torsion angles;200
10.1.12;Summary;202
10.1.13;Further reading;203
10.2;Chapter 16. Electronic charge distribution and potential;204
10.2.1;Charge-density contours;206
10.2.2;Charge in spherical regions;209
10.2.3;Molecular electrostatic potentials;211
10.2.4;Molecular electrostatic potentials of known receptors;214
10.2.5;Displaying potential fields;216
10.2.6;Summary;216
10.2.7;Further reading;217
10.3;Chapter 17. Solvation;218
10.3.1;The supermolecule approach;218
10.3.2;The continuum model;222
10.3.3;The combined approach;224
10.3.4;Simulation methods;225
10.3.5;Status and future of solvent effect calculations;226
10.3.6;Summary;227
10.3.7;Further reading;227
10.4;Chapter 18. Entropy effects;229
10.4.1;Flexible ligands;230
10.4.2;Model calculations;230
10.4.3;Other questions;233
10.4.4;Summary;233
10.4.5;Further reading;234
10.5;Chapter 19. Activity correlations;235
10.5.1;Quantitative structure–activity relationships;235
10.5.2;The potential value of theoretical calculations;236
10.5.3;Anti-allergy agents;239
10.5.4;ß-Lactarn compounds;240
10.5.5;Carcinogenicity of aromatic hydrocarbons;240
10.5.6;Summary;242
10.5.7;Further reading;242
10.6;Chapter 20. Enzymes as receptors;244
10.6.1;Reaction pathways;244
10.6.2;Model enzyme studies;246
10.6.3;Incorporation of many enzyme atoms;247
10.6.4;The study of a series;248
10.6.5;The drug-docking problem;250
10.6.6;Summary;251
10.6.7;Further reading;251
10.7;Chapter 21. Conclusions;252
10.7.1;Can calculations be useful?;252
10.7.2;Is the time ripe?;252
10.7.3;The role of computer graphics;253
10.7.4;How should calculations be used?;254
10.7.5;Moral questions;255
10.7.6;Sub-molecular biology;255
11;Part IV: Bibliography;256
11.1;Bibliography;258
12;Index;284