Kenakin A Pharmacology Primer

Theory, Applications, and Methods
2. Auflage 2010
ISBN: 978-0-08-046530-2
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

E-Book, Englisch, 318 Seiten

The Second Edition will continue this tradition of better preparing researchers in the basics of pharmacology. In addition, new human interest material including historical facts in pharmacology will be added. A new section on therapeutics will help readers identify with diseases and drug treatments.
*Over 30 new figures and tables
*More human interest information to provide readers with historical facts on pharmacology research
*New section on therapeutics to help identify diseaes and drug treatments
*New section on new biological concepts relevant to pharmacological research (i.e., systems biology)
*New study sections organized with ASPET and other international pharmacology organizations
*New coverage of pharmacokinetics and drug disposition

Terry P. Kenakin is the recipient of the 2008 Poulsson Medal for Pharmacology awarded by the Norwegian Society of Pharmacology for achievements in basic and clinical pharmacology and toxicology. He has also been awarded the 2011 Ariens Award from the Dutch Pharmacological Society and the 2014 Gaddum Memorial Award from the British Pharmacological Society. Having been involved in drug discovery for over 30 years, his interests include the optimal design of drug activity assays systems and quantitative drug receptor theory. He is a member of numerous editorial boards as well as Editor-in-Chief of the Journal of Receptors and Signal Transduction and Current Opinion in Pharmacology. In addition, Dr. Kenakin has authored numerous articles and has also written a number of books on pharmacology.

Autoren/Hrsg.

Kenakin, Terry

Inhaltsverzeichnis

1;Front cover;1
2;A PHARMACOLOGY PRIMER THEORY, APPLICATION, AND METHODS;4
3;Copyright page;5
4;Foreword to Second Edition;12
5;Foreword to First Edition;14
6;Table of contents;16
7;Chapter 1. What Is Pharmacology?;20
7.1;1.1 About This Book;20
7.2;1.2 What Is Pharmacology?;20
7.3;1.3 The Receptor Concept;21
7.4;1.4 Pharmacological Test Systems;23
7.5;1.5 The Nature of Drug Receptors;25
7.6;1.6 Pharmacological Intervention and the Therapeutic Landscape;25
7.7;1.7 System-independent Drug Parameters: Affinity and Efficacy;28
7.8;1.8 What Is Affinity?;29
7.9;1.9 The Langmuir Adsorption Isotherm;29
7.10;1.10 What Is Efficacy?;32
7.11;1.11 Dose-response Curves;33
7.12;1.12 Chapter Summary and Conclusions;37
7.13;1.13 Derivations: Conformational Selections as a Mechanism of Efficacy;37
7.14;References;38
8;Chapter 2. How Different Tissues Process Drug Response;40
8.1;2.1 Drug Response as Seen Through the ‘‘Cellular Veil’’;40
8.2;2.2 The Biochemical Nature of Stimulus-response Cascades;42
8.3;2.3 The Mathematical Approximation of Stimulus-response Mechanisms;44
8.4;2.4 System Effects on Agonist Response: Full and Partial Agonists;46
8.5;2.5 Differential Cellular Response to Receptor Stimulus;49
8.6;2.6 Receptor Desensitization and Tachyphylaxis;53
8.7;2.7 The Measurement of Drug Activity;53
8.8;2.8 Advantages and Disadvantages of Different Assay Formats;54
8.9;2.9 Drug Concentration as an Independent Variable;54
8.10;2.10 Chapter Summary and Conclusions;56
8.11;2.11 Derivations;57
8.12;References;58
9;Chapter 3. Drug-Receptor Theory;60
9.1;3.1 About This Chapter;60
9.2;3.2 Drug-Receptor Theory;61
9.3;3.3 The Use of Mathematical Models in Pharmacology;61
9.4;3.4 Some Specific Uses of Models in Pharmacology;62
9.5;3.5 Classical Model of Receptor Function;63
9.6;3.6 The Operational Model of Receptor Function;64
9.7;3.7 Two-state Theory;66
9.8;3.8 The Ternary Complex Model;67
9.9;3.9 The Extended Ternary Model;67
9.10;3.10 Constitutive Receptor Activity;68
9.11;3.11 The Cubic Ternary Complex Model;69
9.12;3.12 Chapter Summary and Conclusions;71
9.13;3.13 Derivations;71
9.14;References;76
10;Chapter 4. Pharmacological Assay Formats: Binding;78
10.1;4.1 The Structure of This Chapter;78
10.2;4.2 Binding Theory and Experiment;78
10.3;4.3 Complex Binding Phenomena: Agonist Affinity from Binding Curves;86
10.4;4.4 Experimental Prerequisites for Correct Application of Binding Techniques;90
10.5;4.5 Chapter Summary and Conclusions;92
10.6;4.6 Derivations;93
10.7;References;96
11;Chapter 5. Agonists: The Measurement of Affinity and Efficacy in Functional Assays;98
11.1;5.1 Functional Pharmacological Experiments;98
11.2;5.2 The Choice of Functional Assays;99
11.3;5.3 Recombinant Functional Systems;103
11.4;5.4 Functional Experiments: Dissimulation in Time;106
11.5;5.5 Experiments in Real Time Versus Stop Time;107
11.6;5.6 The Measurement of Agonist Affinity in Functional Experiments;108
11.7;5.7 Estimates of Relative Efficacy of Agonists in Functional Experiments;114
11.8;5.8 Chapter Summary and Conclusions;115
11.9;5.9 Derivations;115
11.10;References;117
12;Chapter 6. Orthosteric Drug Antagonism;118
12.1;6.1 Introduction;118
12.2;6.2 Kinetics of Drug-Receptor Interaction;118
12.3;6.3 Surmountable Competitive Antagonism;121
12.4;6.4 Noncompetitive Antagonism;133
12.5;6.5 Agonist-Antagonist Hemi-equilibria;136
12.6;6.6 Resultant Analysis;138
12.7;6.7 Chapter Summary and Conclusions;139
12.8;6.8 Derivations;140
12.9;References;145
13;Chapter 7. Allosteric Drug Antagonism;146
13.1;7.1 Introduction;146
13.2;7.2 The Nature of Receptor Allosterism;146
13.3;7.3 Properties of Allosteric Modulators;148
13.4;7.4 Functional Study of Allosteric Modulators;153
13.5;7.5 Measurement of the Potency of Allosteric Insurmountable Antagonists;157
13.6;7.6 Methods for Detecting Allosterism;159
13.7;7.7 Chapter Summary and Conclusions;161
13.8;7.8 Derivations;162
13.9;References;164
14;Chapter 8. The Process of Drug Discovery;166
14.1;8.1 Pharmacology in Drug Discovery;166
14.2;8.2 Chemical Sources for Potential Drugs;166
14.3;8.3 Pharmacodynamics and High-throughput Screening;171
14.4;8.4 Pharmacokinetics;181
14.5;8.5 Pharmaceutical Development;188
14.6;8.6 Adverse Drug Effects;188
14.7;8.7 Chapter Summary and Conclusions;191
14.8;References;191
15;Chapter 9. Target- and System-based Strategies for Drug Discovery;194
15.1;9.1 Some Challenges for Modern Drug Discovery;194
15.2;9.2 Target-based Drug Discovery;194
15.3;9.3 Systems-based Drug Discovery;203
15.4;9.4 In Vivo Systems, Biomarkers, and Clinical Feedback;208
15.5;9.5 Types of Therapeutically Active Ligands;209
15.6;9.6 Summary and Conclusions;212
15.7;References;215
16;Chapter 10. ‘‘Hit’’ to Drug: Lead Optimization;218
16.1;10.1 Tracking SARs and Determining Mechanism of Action: Data-driven Drug-based Pharmacology;218
16.2;10.2 Drug Initiation of Response: Agonism;218
16.3;10.3 Inhibition of Agonist Response: Antagonism;225
16.4;10.4 ‘‘Short-form’’ Measures of Antagonism for Following Structure-activity Relationship;228
16.5;10.5 Summary and Conclusions;237
16.6;10.6 Derivations;237
16.7;References;242
17;Chapter 11. Statistics and Experimental Design;244
17.1;11.1 Structure of This Chapter;244
17.2;11.2 Introduction;244
17.3;11.3 Descriptive Statistics: Comparing Sample Data;244
17.4;11.4 How Consistent Is Experimental Data with Models?;251
17.5;11.5 Comparison of Samples to ‘‘Standard Values’’;268
17.6;11.6 Experimental Design and Quality Control;270
17.7;11.7 Chapter Summary and Conclusions;273
17.8;References;273
18;Chapter 12. Selected Pharmacological Methods;274
18.1;12.1 Binding Experiments;274
18.2;12.2 Functional Experiments;276
19;Glossary of Pharmacological Terms;296
20;Appendices;302
20.1;A.1 Statistical Tables of Use for Assessing Significant Difference;302
20.2;A.2 Mathematical Fitting Functions;306
21;Index;312