Richard A. Glennon, Richard Young

Drug Discrimination

Applications to Medicinal Chemistry and Drug Studies
Herausgeber: Glennon, Richard A; Young, Richard

• Gebundenes Buch

Produktbeschreibung

Although somewhat labor intensive, Drug Discrimination (DD) is of enormous applicability to the understanding of drug action. Drug Discrimination: Applications to Medicinal Chemistry and Drug Studies covers the practical applications of drug discrimination studies for medicinal chemistry, including strengths and limitations versus other pharmacological methods for evaluating drug action. The book provides medicinal chemists with a fuller understanding of the nature and use of drug discrimination studies for evaluating the action of drugs while helping pharmacologists understand and better interact with medicinal chemists and drug designers when sharing pharmacologic data.

Produktdetails

• Verlag: Wiley & Sons
• 1. Auflage
• Seitenzahl: 530
• Erscheinungstermin: 23. August 2011
• Englisch
• Abmessung: 236mm x 157mm x 33mm
• Gewicht: 930g
• ISBN-13: 9780470433522
• ISBN-10: 0470433523
• Artikelnr.: 33612504

Autorenporträt

Richard Glennon is Chair of the Department of Medicinal Chemistry at Virginia Commonwealth University. He is the author of over four hundred scientific publications and book chapters. Richard Young is an Associate Professor in the Department of Medicinal Chemistry at Virginia Commonwealth University. Previously, he worked in the pharmaceutical industry at Ayerst and A. H. Robins (both now Pfizer).

Inhaltsangabe

Preface xv Contributors xix Part I 1 Richard A. Glennon and Richard Young
1. An Introduction to Drug Discrimination 3 A. General Scope and
Introductory Comments 3 B. Background and Utility of the Drug
Discrimination Paradigm 7 C. Drug Discrimination: A Synopsis of the
Approach 10 D. Drug Discrimination and Drugs of Abuse 11 E. Advantage of
the Drug Discrimination Procedure 14 2. Methodological Considerations 19 A.
Apparatus 19 B. Subjects 22 C. Operant Conditioning 23 3. Drug
Discrimination: Practical Considerations 41 A. Drugs as Discriminative
Stimuli 42 B. Choice of Dose and Pre-session Injection Interval 49 C.
Discrimination Training Procedure 51 D. Discrimination Data 52 E. Testing
60 F. Data Analysis and Interpretations 78 G. Selected Topics 99 4. Role of
Stereochemistry in Drug Discrimination Studies 129 A. Structural Isomers:
Introduction 129 B. Constitutional Isomers 130 C. Stereoisomers 136 5. Drug
Discrimination and in Vivo Structure-Activity Relationships 163 A.
Structure-Activity Caveats 163 B. Phenylalkylamines Hallucinogens and
Stimulants 165 C. Benzodiazepines 175 D. Neuronal Nicotinic
Acetylcholinergic receptor Agents 177 E. Aminotetralins 178 6. Drug
Discrimination and Mechanisms of Drug Action 183 A. Early Considerations
184 B. Classical Hallucinogens 186 C. Amphetamine-Related Stimulants 192 D.
MDA and MDMA 198 E. PMMA 204 F. a-Ethyltryptamine 205 G. Anxiolytic Agents
206 7. Drug Discrimination and Development of Novel Agents and
Pharmacological Tools 217 A. Applicability and General Comments 217 B.
Novel 5-HT2 Serotonin Receptor Antagonists 218 C. 5-HT2 Serotonin Receptor
Agonists and Radioligands 222 D. Aminotetralins as 5-HT1A Serotonin
Receptor Ligands 225 E. Arylpiperazine 5-HT1A Serotonin Receptor
Antagonists 225 F. MD-354 (meta-Chlorophenylguanidine): A 5-HT3 Serotonin
Receptor Agonist 227 G. Loperamide and Risperidone: Clinical Successes 230
Appendix 235 Part II 239 8. Perceptual Drug Discriminative Aspects of the
Endocannabinoid Signaling System in Animals and Man 241 Torbjörn U. C.
Järbe A. Introduction 242 B. Brief Synopsis of the Endocannabinoid
Signaling System (ECS) 243 C. Cannabinoids/Cannabinergics and Drug
Discrimination 244 D. Experimental Procedures and Species 244 E. Training
Drugs 247 F. Procedural Considerations 253 G. Intended and Unintended
"Bias" in Drug Discrimination 254 H. Origin of the Drug Stimulus and
Sensory Mediation 254 I. Acquired Differences in Drug Sensitivity 255 J.
Pharmacological Specificity 258 K. Phytocannabinoids and Metabolites 260 L.
Endocannabinoid Ligands and the ECS 262 M. ECS Interactions with Other
Signaling Systems 265 N. Conclusions/Summary 266 O. Addendum 268 9.
Discriminative Stimulus Properties of Receptor Antagonists 287 Joseph H.
Porter A. Introduction 288 B. Adrenoceptor Antagonists 289 C.
Antihistamines 292 D. Atypical Antipsychotic Drugs 294 E. Benzodiazepine
Antagonists 299 F. Cannabinoid Antagonists 299 G. Cholinergic Antagonists
301 H. Dopamine Antagonists 302 I. GABAergic Antagonists 305 J. Opiate
Antagonists 306 K. Serotonergic Anatagonists 310 L. Summary 312 10. The
Discrimination of Drug Mixtures 323 Ian P. Stolerman A. Introduction 324 B.
Functional Models for the Discriminative Effects of Drug Mixtures 326 C.
Initial Studies: Mixtures of Nicotine plus Midazolam 328 D. Characteristics
of Diverse Drug Discriminations 329 E. Role of Training Doses 334 F.
Variations in Functional Relationships: The Role of Training Paradigm 336
G. Antagonism of Mixture Cues and Training with Agonists plus Antagonists
342 H. Associative Processes 345 I. Investigations on the Ethanol Cue as a
Compound Stimulus 348 J. Discussion 351 11. Making the Right Choice:
Lessons from Drug Discrimination for Research on Drug Reinforcement and
Drug Self-Administration 361 S. Stevens Negus and Matthew L. Banks A.
Operant Conditioning to Study the Stimulus Properties of Drugs 362 B.
Choice Procedures in Studies of Drug Reinforcement: Lessons from Drug
Discrimination 371 C. Summary 380 12. Inhalant Drug Discrimination Studies
in Phesus Monkeys: Drug Dependence and Withdrawal 417 Jun-Xu Li, Lisa R.
Gerak, and Charles P. France A. Introduction 417 B. Some Factors Impacting
the Discriminative Stimulus Effects of Drugs 418 C. Drug Interactions:
Acute Dosing 420 D. Drug Interactions: Chronic Dosing 423 E. Summary and
Conclusions 427 14. Human Drug Discrimination: Methodological
Considerations and Application to Elucidating the Neuropharmacology of
Amphetamines 431 Craig R. Rush, Andrea R. Vansickel, and William W. Stoops
A. Introduction 432 B. Methodological Issues to Consider when Designing and
Conducting a Human Drug Discrimination Experiment 433 C. Using Human Drug
Discrimination to Elucidate the Neuropharmacology of Amphetamines 444 D.
The Future of Human Drug Discrimination 449 15. Nicotine Discrimination in
Humans 463 Kenneth A. Perkins A. Introduction 464 B. Basic Methods of
Nicotine Discrimination Research in Humans 465 C. Basic Parameters of
Nicotine Discrimination 468 D. Individual Differences and Moderators of
Nicotine Discrimination 473 E. Conclusions 477 16. Drug Discrimination: A
Perspective 483 The late Francis C. Colpaert A. State Dependence and Drug
Discrimination 484 B. Drug Discrimination in Receptor Pharmacology 484 C.
Drug Discrimination and Subjective Drug Effects 485 D. New Concepts of
Opiate Tolerance, Signal Processing, Pain, and Analgesia 486 E. Drug
Discrimination: An Elementary Particle of Behavior and More 488 F. When
Dependent Variables Chose Their Pharmacology 491 G. Two Further Mysteries
491 H. Epilogue 492 Index 497