Muutke küpsiste eelistusi

Pharmacology Primer: Techniques for More Effective and Strategic Drug Discovery 4th edition [Kõva köide]

(Professor, Pharmacology, University of North Carolina, USA)
  • Formaat: Hardback, 450 pages, kõrgus x laius: 276x216 mm, kaal: 1500 g, 100 illustrations (100 in full color); Illustrations, unspecified
  • Ilmumisaeg: 08-Apr-2014
  • Kirjastus: Academic Press Inc
  • ISBN-10: 0124076637
  • ISBN-13: 9780124076631
Teised raamatud teemal:
Pharmacology Primer: Techniques for More Effective and Strategic Drug Discovery 4th editionSuurem pilt
  • Formaat: Hardback, 450 pages, kõrgus x laius: 276x216 mm, kaal: 1500 g, 100 illustrations (100 in full color); Illustrations, unspecified
  • Ilmumisaeg: 08-Apr-2014
  • Kirjastus: Academic Press Inc
  • ISBN-10: 0124076637
  • ISBN-13: 9780124076631
Teised raamatud teemal:
Püsilink: https://www.kriso.ee/db/9780124076631.html
Märksõnad:
This book details the methods and tools used in pharmacology to quantify drug activity to improve the effectiveness of drug discovery. Each chapter explains basic concepts, techniques used to estimate drug parameters, and the mathematical derivations of the models used. They describe pharmacology, how different tissues process drug response, drug-receptor theory, binding techniques, agonists, orthosteric drug antagonism, allosteric modulation, the optimal design of pharmacological experiments, pharmacokinetics, safety, the drug discovery process, statistics and experimental design, and selected pharmacological methods (binding and functional assays), ending with exercises in pharmacodynamics and pharmacokinetics. This edition has discussion of the new trend in drug discovery that considers pharmacokinetics and absorption, distribution, metabolism, and excretion properties of drugs early in the process, and spans pharmacology from the independent to the dependent variable. It has material on data-driven drug discovery, biased signaling, structure-based drug design, drug activity screening, drug development, and other topics. Annotation ©2014 Ringgold, Inc., Portland, OR (protoview.com) A Pharmacology Primer: Techniques for More Effective and Strategic Drug Discovery, 4th Edition features the latest ideas and research about the application of pharmacology to the process of drug discovery to equip readers with a deeper understanding of the complex and rapid changes in this field. Written by well-respected pharmacologist, Terry P. Kenakin, this primer is an indispensable resource for all those involved in drug discovery. This edition has been thoroughly revised to include material on data-driven drug discovery, biased signaling, structure-based drug design, drug activity screening, drug development (including pharmacokinetics and safety Pharmacology), and much more. With more color illustrations, examples, and exercises throughout, this book remains a top reference for all industry and academic scientists and students directly involved in drug discovery, or pharmacologic research. Highlights changes surrounding the strategy of drug discovery to provide you with a comprehensive reference featuring advances in the methods involved in lead optimization and more effective drug discoveryIncludes a new chapter on data-driven drug discovery in terms of the optimal design of pharmacological experiments to identify mechanism of action of new moleculesIllustrates the application of rapid inexpensive assays to predict activity in the therapeutic setting, showing data outcomes and the limitations inherent in interpreting this data

Arvustused

"This edition adds solid overviews of emerging topics in the field...which keep it at the cutting edge of receptor pharmacology...a valuable resource for students of pharmacology and all members of drug discovery and design teams. Rating: 4 Stars" --Doody's.com, Sep 2014

"a major strength of the present monograph is the authors long-standing commitment to the didactic promotion of the discipline of pharmacology as the primary, unifying discipline of drug discovery. This monograph remains the key reference work in pharmacology and receptor theory, providing an irreplaceable yet accessible reference source for all scientists involved in biomedical research as it pertains to drug discovery." --Drug Development Research, June 2014

"A wonderful contribution to the world of pharmacology that takes the reader from introductory information to advanced receptor theory. This book will be useful to both students and seasoned researchers alike. Beautifully illustrated and clearly written, this book is a welcome addition to every library." --P Michael Conn, PhD, Senior Vice President for Research and Associate Provost, Professor of Internal Medicine, School of Medicine, Professor of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, TX

Muu info

Authored by world-renowned pharmacologist, Terry P. Kenakin, the 4th edition of the Primer focuses on advances in structure based drug design, data-driven drug discovery and screening technologies to provide the optimal resource for all those involved in drug discovery
Preface xiii
Preface to the Third Edition xv
Preface to the Second Edition xvii
Preface to the First Edition xix
1 What Is Pharmacology?
1.1 About This Book
1(1)
1.2 What Is Pharmacology?
1(2)
1.3 The Receptor Concept
3(2)
1.4 Pharmacological Test Systems
5(2)
1.5 The Nature of Drug Receptors
7(1)
1.6 Pharmacological Intervention and the Therapeutic Landscape
8(1)
1.7 System-Independent Drug Parameters: Affinity and Efficacy
9(2)
1.8 What is Affinity?
11(2)
1.9 The Langmuir Adsorption Isotherm
13(2)
1.10 What is Efficacy?
15(1)
1.11 Dose-Response Curves
16(3)
1.11.1 Potency and Maximal Response
17(1)
1.11.2 p-Scales and the Representation of Potency
18(1)
1.12
Chapter Summary and Conclusions
19(1)
1.13 Derivations: Conformational Selection as a Mechanism of Efficacy
20(1)
References
20(1)
2 How Different Tissues Process Drug Response
2.1 Drug Response as Seen Through the "Cellular Veil"
21(2)
2.2 The Biochemical Nature of Stimulus-Response Cascades
23(2)
2.3 The Mathematical Approximation of Stimulus-Response Mechanisms
25(2)
2.4 System Effects on Agonist Response: Full and Partial Agonists
27(3)
2.5 Differential Cellular Response to Receptor Stimulus
30(5)
2.5.1 Choice of Response Pathway
31(1)
2.5.2 Augmentation or Modulation of Stimulus Pathway
31(1)
2.5.3 Differences in Receptor Density
32(1)
2.5.4 Target-Mediated Trafficking of Stimulus
33(2)
2.6 Receptor Desensitization and Tachyphylaxis
35(2)
2.7 The Measurement of Drug Activity
37(1)
2.8 Advantages and Disadvantages of Different Assay Formats
37(1)
2.9 Drug Concentration as an Independent Variable
38(2)
2.9.1 Dissimulation in Drug Concentration
38(2)
2.9.2 Free Concentration of Drug
40(1)
2.10
Chapter Summary and Conclusions
40(1)
2.11 Derivations
41(4)
2.11.1 Series Hyperbolae Can Be Modeled by a Single Hyperbolic Function
41(1)
2.11.2 Successive Rectangular Hyperbolic Equations Necessarily Lead to Amplification
41(1)
2.11.3 Saturation of Any Step in a Stimulus Cascade by Two Agonists Leads to Identical Maximal Final Responses for the Two Agonists
41(1)
2.11.4 Procedure to Measure Free Drug Concentration in the Receptor Compartment
42(1)
References
42(3)
3 Drug-Receptor Theory
3.1 About This
Chapter
45(1)
3.2 Drug-Receptor Theory
46(1)
3.3 The Use of Mathematical Models in Pharmacology
47(1)
3.4 Some Specific Uses of Models in Pharmacology
47(2)
3.5 Classical Model of Receptor Function
49(1)
3.6 The Operational Model of Receptor Function
50(1)
3.7 Two-State Theory
51(1)
3.8 The Ternary Complex Model
52(1)
3.9 The Extended Ternary Complex Model
52(1)
3.10 Constitutive Receptor Activity and Inverse Agonism
53(2)
3.11 The Cubic Ternary Complex Model
55(1)
3.12 Multistate Receptor Models and Probabilistic Theory
56(1)
3.13
Chapter Summary and Conclusions
57(1)
3.14 Derivations
57(6)
3.14.1 Radioligand Binding to Receptor Dimers Demonstrating Cooperative Behavior
58(1)
3.14.2 Effect of Variation in an HIV-1 Binding Model
58(1)
3.14.3 Derivation of the Operational Model
59(1)
3.14.4 Operational Model Forcing Function for Variable Slope
60(1)
3.14.5 Derivation of Two-State Theory
60(1)
3.14.6 Derivation of the Extended Ternary Complex Model
61(1)
3.14.7 Dependence of Constitutive Activity on Receptor Density
61(1)
3.14.8 Derivation of the Cubic Ternary Complex Model
61(1)
References
62(1)
4 Pharmacological Assay Formats: Binding
4.1 The Structure of This
Chapter
63(1)
4.2 Binding Theory and Experiment
63(9)
4.2.1 Saturation Binding
65(2)
4.2.2 Displacement Binding
67(4)
4.2.3 Kinetic Binding Studies
71(1)
4.3 Complex Binding Phenomena: Agonist Affinity from Binding Curves
72(3)
4.4 Experimental Prerequisites for Correct Application of Binding Techniques
75(3)
4.4.1 The Effect of Protein Concentration on Binding Curves
75(2)
4.4.2 The Importance of Equilibration Time for Equilibrium between Two Ligands
77(1)
4.5
Chapter Summary and Conclusions
78(1)
4.6 Derivations
79(6)
4.6.1 Displacement Binding: Competitive Interaction
79(1)
4.6.2 Displacement Binding: Noncompetitive Interaction
79(1)
4.6.3 Displacement of a Radioligand by an Allosteric Antagonist
80(1)
4.6.4 Relationship between IC50 and K1 for Competitive Antagonists
80(1)
4.6.5 Maximal Inhibition of Binding by an Allosteric Antagonist
81(1)
4.6.6 Relationship between IC50 and K1 for Allosteric Antagonists
81(1)
4.6.7 Two-Stage Binding Reactions
81(1)
4.6.8 Effect of G-protein Coupling on Observed Agonist Affinity
82(1)
4.6.9 Effect of Excess Receptor in Binding Experiments: Saturation Binding Curve
82(1)
4.6.10 Effect of Excess Receptor in Binding Experiments: Displacement Experiments
82(1)
References
82(3)
5 Agonists: The Measurement of Affinity and Efficacy in Functional Assays
5.1 Functional Pharmacological Experiments
85(1)
5.2 The Choice of Functional Assays
86(4)
5.3 Recombinant Functional Systems
90(3)
5.4 Functional Experiments: Dissimulation in Time
93(2)
5.5 Experiments in Real Time Versus Stop-Time
95(1)
5.6 Quantifying Agonism: The Black-Leff Operational Model of Agonism
96(6)
5.6.1 Affinity-Dependent versus Efficacy-Dependent Agonist Potency
98(3)
5.6.2 Secondary and Tertiary Testing of Agonists
101(1)
5.7 Biased Signaling
102(5)
5.7.1 Receptor Selectivity
107(1)
5.8 Null Analyses of Agonism
107(7)
5.8.1 Partial Agonists
107(3)
5.8.2 Full Agonists
110(4)
5.9
Chapter Summary and Conclusions
114(1)
5.10 Derivations
114(5)
5.10.1 Relationship Between the EC50 and Affinity of Agonists
114(1)
5.10.2 Method of Barlow, Scott, and Stephenson for Affinity of Partial Agonists
115(1)
5.10.3 Maximal Response of a Partial Agonist Is Dependent on Efficacy
115(1)
5.10.4 System Independence of Full Agonist Potency Ratios
115(1)
5.10.5 Measurement of Agonist Affinity: Method of Furchgott
115(1)
References
116(3)
6 Orthosteric Drug Antagonism
6.1 Introduction
119(1)
6.2 Kinetics Of Drug-Receptor Interaction
120(2)
6.3 Surmountable Competitive Antagonism
122(12)
6.3.1 Schild Analysis
122(4)
6.3.2 Patterns of Dose-Response Curves That Preclude Schild Analysis
126(1)
6.3.3 Best Practice for the Use of Schild Analysis
127(1)
6.3.4 Analyses for Inverse Agonists in Constitutively Active Receptor Systems
128(3)
6.3.5 Analyses for Partial Agonists
131(2)
6.3.6 The Method of Lew and Angus: Nonlinear Regressional Analysis
133(1)
6.4 Noncompetitive Antagonism
134(4)
6.5 Agonist-Antagonist Hemi-Equilibria
138(1)
6.6 Resultant Analysis
139(2)
6.7 Antagonist Receptor Coverage: Kinetics of Dissociation
141(3)
6.7.1 Estimating Antagonist Dissociation with Hemi-Equilibria
142(2)
6.8 Blockade of Indirectly Acting Agonists
144(1)
6.9 Irreversible Antagonism
144(2)
6.10 Chemical Antagonism
146(3)
6.11
Chapter Summary and Conclusions
149(1)
6.12 Derivations
149(6)
6.12.1 Derivation of the Gaddum Equation for Competitive Antagonism
149(1)
6.12.2 Derivation of the Gaddum Equation for Noncompetitive Antagonism
150(1)
6.12.3 Derivation of the Schild Equation
150(1)
6.12.4 Functional Effects of an Inverse Agonist with the Operational Model
150(1)
6.12.5 pA2 Measurement for Inverse Agonists
151(1)
6.12.6 Functional Effects of a Partial Agonist with the Operational Model
151(1)
6.12.7 pA2 Measurements for Partial Agonists
151(1)
6.12.8 Method of Stephenson for Partial Agonist Affinity Measurement
152(1)
6.12.9 Derivation of the Method of Gaddum for Noncompetitive Antagonism
152(1)
6.12.10 Relationship of pA2 and pKB for Insurmountable Orthosteric Antagonism
152(1)
6.12.11 Resultant Analysis
153(1)
6.12.12 Blockade of Indirectly Acting Agonists
153(1)
6.12.13 Chemical Antagonism: Abstraction of Agonist Concentration
153(1)
6.12.14 Chemical Antagonism: Abstraction of Antagonist Concentration
154(1)
References
154(1)
7 Allosteric Modulation
7.1 Introduction
155(1)
7.2 The Nature of Receptor Allosterism
155(3)
7.3 Unique Effects of Allosteric Modulators
158(4)
7.4 Functional Study of Allosteric Modulators
162(13)
7.4.1 Phenotypic Allosteric Modulation Profiles
166(1)
7.4.2 Allosteric Agonism
166(1)
7.4.3 Affinity of Allosteric Modulators
167(1)
7.4.4 Negative Allosteric Modulators (NAMs)
168(4)
7.4.5 Positive Allosteric Modulators (PAMs)
172(2)
7.4.6 Optimal Assays for Allosteric Function
174(1)
7.5 Methods for Detecting Allosterism
175(2)
7.6
Chapter Summary and Conclusions
177(1)
7.7 Derivations
178(3)
7.7.1 Allosteric Model of Receptor Activity
178(1)
7.7.2 Effects of Allosteric Ligands on Response: Changing Efficacy
178(1)
7.7.3 Schild Analysis for Allosteric Antagonists
179(1)
References
179(2)
8 The Optimal Design of Pharmacological Experiments
8.1 Introduction
181(1)
8.2 The Optimal Design of Pharmacological Experiments
181(16)
8.2.1 Drug Efficacy
182(6)
8.2.2 Affinity
188(7)
8.2.3 Orthosteric vs. Allosteric Mechanisms
195(1)
8.2.4 Target Coverage In Vivo
196(1)
8.3 Null Experiments and Fitting Data to Models
197(2)
8.4 Interpretation of Experimental Data
199(3)
8.5 Predicting Therapeutic Activity in All Systems
202(6)
8.5.1 Predicting Agonism
203(1)
8.5.2 Predicting Binding
204(2)
8.5.3 Kinetics of Target Coverage
206(1)
8.5.4 Drug Combinations In Vivo
206(2)
8.6 Summary and Conclusions
208(1)
8.7 Derivations
209(4)
8.7.1 IC50 Correction Factors: Competitive Antagonists
209(1)
8.7.2 Relationship of pA2 and pKB for Insurmountable Orthosteric Antagonism
209(1)
8.7.3 Relationship of pA2 and pKB for Insurmountable Allosteric Antagonism
210(1)
References
210(3)
9 Pharmacokinetics
9.1 Introduction
213(1)
9.2 Biopharmaceutics
213(1)
9.3 The Chemistry of "Druglike" Character
214(4)
9.4 Pharmacokinetics
218(25)
9.4.1 Drug Absorption
219(6)
9.4.2 Route of Drug Administration
225(2)
9.4.3 General Pharmacokinetics
227(2)
9.4.4 Metabolism
229(3)
9.4.5 Clearance
232(2)
9.4.6 Volume of Distribution and Half Life
234(6)
9.4.7 Renal Clearance
240(2)
9.4.8 Bioavailability
242(1)
9.5 Nonlinear Pharmacokinetics
243(1)
9.6 Multiple Dosing
244(3)
9.7 Practical Pharmacokinetics
247(2)
9.7.1 Allometric Scaling
247(2)
9.8 Placement of Pharmacokinetic Assays in Discovery and Development
249(3)
9.9 Summary and Conclusions
252(3)
References
253(2)
10 Safety Pharmacology
10.1 Safety Pharmacology
255(6)
10.2 Hepatotoxicity
261(10)
10.2.1 Drug-Drug Interactions
261(9)
10.2.2 Direct Hepatotoxicity
270(1)
10.3 Cytotoxicity
271(1)
10.4 Mutagenicity
272(1)
10.5 hERG Activity and Torsades De Pointes
273(1)
10.6 Autonomic Receptor Profiling
273(1)
10.7 General Pharmacology
274(1)
10.8 Clinical Testing
274(4)
10.9 Summary and Conclusions
278(3)
References
279(2)
11 The Drug Discovery Process
11.1 Some Challenges for Modem Drug Discovery
281(1)
11.2 Target-Based Drug Discovery
282(9)
11.2.1 Target Validation and the Use of Chemical Tools
283(2)
11.2.2 Recombinant Systems
285(1)
11.2.3 Defining Biological Targets
286(5)
11.3 Systems-Based Drug Discovery
291(5)
11.3.1 Assays in Context
294(2)
11.4 In vivo Systems, Biomarkers, and Clinical Feedback
296(1)
11.5 Types of Therapeutically Active Ligands: Polypharmacology
297(3)
11.6 Pharmacology in Drug Discovery
300(2)
11.7 Chemical Sources for Potential Drugs
302(5)
11.8 Pharmacodynamics and High-Throughput Screening
307(7)
11.9 Drug Development
314(2)
11.10 Clinical Testing
316(2)
11.11 Summary and Conclusions
318(3)
References
318(3)
12 Statistics and Experimental Design
12.1 Structure of This
Chapter
321(1)
12.2 Introduction
321(1)
12.3 Descriptive Statistics: Comparing Sample Data
321(9)
12.3.1 Gaussian Distribution
322(1)
12.3.2 Populations and Samples
322(2)
12.3.3 Confidence Intervals
324(1)
12.3.4 Paired Data Sets
325(1)
12.3.5 One-Way Analysis of Variance
326(1)
12.3.6 Two-Way Analysis of Variance
327(1)
12.3.7 Regression and Correlation
327(2)
12.3.8 Detection of Single Versus Multiple Populations
329(1)
12.4 How Consistent are Experimental Data with Models?
330(16)
12.4.1 Comparison of Data to Models: Choice of Model
330(2)
12.4.2 Curve Fitting: Good Practice
332(2)
12.4.3 Outliers and Weighting Data Points
334(2)
12.4.4 Overextrapolation of Data
336(1)
12.4.5 Hypothesis Testing: Examples with Dose-Response Curves
337(3)
12.4.6 One Curve or Two? Detection of Differences in Curves
340(1)
12.4.7 Asymmetrical Dose-Response Curves
341(1)
12.4.8 Comparison of Data to Linear Models
342(1)
12.4.9 Is a Given Regression Linear?
342(1)
12.4.10 One or More Regression Lines? Analysis of Covariance
343(3)
12.5 Comparison of Samples to "Standard Values"
346(1)
12.5.1 Comparison of Means by Two Methods or in Two Systems
346(1)
12.5.2 Comparing Assays/Methods with a Range of Ligands
347(1)
12.6 Experimental Design and Quality Control
347(3)
12.6.1 Detection of Difference in Samples
347(1)
12.6.2 Power Analysis
348(2)
12.7
Chapter Summary and Conclusions
350(1)
References
350(1)
13 Selected Pharmacological Methods
13.1 Binding Experiments
351(2)
13.1.1 Saturation Binding
351(1)
13.1.2 Displacement Binding
351(2)
13.2 Functional Assays
353(20)
13.2.1 Determination of Equiactive Concentrations on Dose-Response Curves
353(2)
13.2.2 Method of Barlow, Scott, and Stephenson for Measurement of the Affinity of a Partial Agonist
355(1)
13.2.3 Method of Furchgott for the Measurement of the Affinity of a Full Agonist
356(1)
13.2.4 Schild Analysis for the Measurement of Competitive Antagonist Affinity
357(2)
13.2.5 Method of Stephenson for Measurement of Partial Agonist Affinity
359(2)
13.2.6 Method of Gaddum for Measurement of Noncompetitive Antagonist Affinity
361(1)
13.2.7 Method for Estimating Affinity of Insurmountable Antagonist (Dextral Displacement Observed)
362(1)
13.2.8 Resultant Analysis for Measurement of Affinity of Competitive Antagonists with Multiple Properties
363(1)
13.2.9 Measurement of the Affinity and Maximal Allosteric Constant for Allosteric Modulators Producing Surmountable Effects
364(4)
13.2.10 Method for Estimating Affinity of Insurmountable Antagonist (No Dextral Displacement Observed): Detection of Allosteric Effect
368(1)
13.2.11 Measurement of pKB for Competitive Antagonists from a plC50
369(4)
14 Exercises in Pharmacodynamics and Pharmacokinetics
14.1 Introduction
373(1)
14.2 Agonism
373(10)
14.2.1 Agonism: Structure-Activity Relationships
373(1)
14.2.2 Prediction of Agonist Effect
374(1)
14.2.3 "Super Agonists"
375(1)
14.2.4 Atypical Agonists
376(1)
14.2.5 Ordering of Affinity and Efficacy in Agonist Series
376(1)
14.2.6 Kinetics of Agonism
376(1)
14.2.7 Affinity-Dominant versus Efficacy-Dominant Agonists
377(2)
14.2.8 Agonist Affinities and Potencies Do Not Correlate
379(1)
14.2.9 Lack of Agonist Effect
380(2)
14.2.10 Assay-Specific Agonism
382(1)
14.3 Antagonism
383(8)
14.3.1 Antagonist Potency and Kinetics: Part A
383(2)
14.3.2 Antagonist Potency in plC50 Format (Kinetics Part B)
385(1)
14.3.3 Mechanism of Antagonist Action (Kinetics Part C)
386(1)
14.3.4 Mechanism of Antagonist Action: Curve Patterns
386(1)
14.3.5 Mechanism of Action: Incomplete Antagonism
387(2)
14.3.6 plC50 Mode: Antagonism Below Basal
389(1)
14.3.7 Secondary Effects of Antagonists
390(1)
14.3.8 Antagonist Potency Variably Dependent on Agonist Concentration
390(1)
14.4 In vitro--In vivo Transitions and General Discovery
391(5)
14.4.1 "Silent Antagonism"
391(1)
14.4.2 Loss of Activity
392(1)
14.4.3 Marking Relevant Agonism
393(1)
14.4.4 In vitro---In vivo Correspondence of Activity
394(1)
14.4.5 Divergent Agonist-Dependent Antagonism
395(1)
14.5 SAR Exercises
396(1)
14.5.1 Surrogate Screens
396(1)
14.6 Pharmacokinetics
397(5)
14.6.1 Clearance
397(2)
14.6.2 Drug-Drug Interactions
399(1)
14.6.3 Distribution I
399(1)
14.6.4 Distribution II
399(1)
14.6.5 Half Life I
399(1)
14.6.6 Half Life II
400(1)
14.6.7 Half Life III
400(1)
14.6.8 Renal Clearance I
400(1)
14.6.9 Renal Clearance II
400(1)
14.6.10 Renal Clearance III
401(1)
14.6.11 Absorption
401(1)
14.6.12 Predictive Pharmacokinetics I
401(1)
14.6.13 Predictive Pharmacokinetics II
401(1)
14.6.14 Predictive Pharmacokinetics III
401(1)
14.6.15 Log D and Pharmacokinetics
401(1)
14.7 Conclusions
402(1)
References
402(1)
Appendices
403(12)
A.1 Statistical Tables of Use for Assessing Significant Difference
403(8)
A.2 Mathematical Fitting Functions
411(4)
Glossary of Pharmacological Terms 415(6)
Index 421
Dr. Terry Kenakin is Professor of Pharmacology at the University of North Carolina School of Medicine. Prior to this, he spent 7 years in drug discovery at Burroughs-Wellcome. He then moved to GlaxoSmithKline for 25 years. Dr. Kenakin has written 11 books on Pharmacology, is the Editor in Chief of the Journal of Receptors and Signal Transduction, is on numerous Editorial Boards. He is the Editor-in-Chief of Comprehensive Pharmacology (Elsevier, 2022). He 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, and the 2020 Goodman and Gilman Award in Receptor Pharmacology from ASPET.