Drug Discrimination

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).

• Preface xv Contributors xixPart I 1Richard A. Glennon and Richard Young1. An Introduction to Drug Discrimination 3A. General Scope and Introductory Comments 3B. Background and Utility of the Drug Discrimination Paradigm 7C. Drug Discrimination: A Synopsis of the Approach 10D. Drug Discrimination and Drugs of Abuse 11E. Advantage of the Drug Discrimination Procedure 142. Methodological Considerations 19A. Apparatus 19B. Subjects 22C. Operant Conditioning 233. Drug Discrimination: Practical Considerations 41A. Drugs as Discriminative Stimuli 42B. Choice of Dose and Pre-session Injection Interval 49C. Discrimination Training Procedure 51D. Discrimination Data 52E. Testing 60F. Data Analysis and Interpretations 78G. Selected Topics 994. Role of Stereochemistry in Drug Discrimination Studies 129A. Structural Isomers: Introduction 129B. Constitutional Isomers 130C. Stereoisomers 1365. Drug Discrimination and in Vivo Structure-Activity Relationships 163A. Structure-Activity Caveats 163B. Phenylalkylamines Hallucinogens and Stimulants 165C. Benzodiazepines 175D. Neuronal Nicotinic Acetylcholinergic receptor Agents 177E. Aminotetralins 1786. Drug Discrimination and Mechanisms of Drug Action 183A. Early Considerations 184B. Classical Hallucinogens 186C. Amphetamine-Related Stimulants 192D. MDA and MDMA 198E. PMMA 204F. a-Ethyltryptamine 205G. Anxiolytic Agents 2067. Drug Discrimination and Development of Novel Agents and Pharmacological Tools 217A. Applicability and General Comments 217B. Novel 5-HT2 Serotonin Receptor Antagonists 218C. 5-HT2 Serotonin Receptor Agonists and Radioligands 222D. Aminotetralins as 5-HT1A Serotonin Receptor Ligands 225E. Arylpiperazine 5-HT1A Serotonin Receptor Antagonists 225F. MD-354 (meta-Chlorophenylguanidine): A 5-HT3 Serotonin Receptor Agonist 227G. Loperamide and Risperidone: Clinical Successes 230Appendix 235Part II 2398. Perceptual Drug Discriminative Aspects of the Endocannabinoid Signaling System in Animals and Man 241Torbjörn U. C. JärbeA. Introduction 242B. Brief Synopsis of the Endocannabinoid Signaling System (ECS) 243C. Cannabinoids/Cannabinergics and Drug Discrimination 244D. Experimental Procedures and Species 244E. Training Drugs 247F. Procedural Considerations 253G. Intended and Unintended “Bias” in Drug Discrimination 254H. Origin of the Drug Stimulus and Sensory Mediation 254I. Acquired Differences in Drug Sensitivity 255J. Pharmacological Specificity 258K. Phytocannabinoids and Metabolites 260L. Endocannabinoid Ligands and the ECS 262M. ECS Interactions with Other Signaling Systems 265N. Conclusions/Summary 266O. Addendum 2689. Discriminative Stimulus Properties of Receptor Antagonists 287Joseph H. PorterA. Introduction 288B. Adrenoceptor Antagonists 289C. Antihistamines 292D. Atypical Antipsychotic Drugs 294E. Benzodiazepine Antagonists 299F. Cannabinoid Antagonists 299G. Cholinergic Antagonists 301H. Dopamine Antagonists 302I. GABAergic Antagonists 305J. Opiate Antagonists 306K. Serotonergic Anatagonists 310L. Summary 31210. The Discrimination of Drug Mixtures 323Ian P. StolermanA. Introduction 324B. Functional Models for the Discriminative Effects of Drug Mixtures 326C. Initial Studies: Mixtures of Nicotine plus Midazolam 328D. Characteristics of Diverse Drug Discriminations 329E. Role of Training Doses 334F. Variations in Functional Relationships: The Role of Training Paradigm 336G. Antagonism of Mixture Cues and Training with Agonists plus Antagonists 342H. Associative Processes 345I. Investigations on the Ethanol Cue as a Compound Stimulus 348J. Discussion 35111. Making the Right Choice: Lessons from Drug Discrimination for Research on Drug Reinforcement and Drug Self-Administration 361S. Stevens Negus and Matthew L. BanksA. Operant Conditioning to Study the Stimulus Properties of Drugs 362B. Choice Procedures in Studies of Drug Reinforcement: Lessons from Drug Discrimination 371C. Summary 38012. Inhalant Drug Discrimination Studies in Phesus Monkeys: Drug Dependence and Withdrawal 417Jun-Xu Li, Lisa R. Gerak, and Charles P. FranceA. Introduction 417B. Some Factors Impacting the Discriminative Stimulus Effects of Drugs 418C. Drug Interactions: Acute Dosing 420D. Drug Interactions: Chronic Dosing 423E. Summary and Conclusions 42714. Human Drug Discrimination: Methodological Considerations and Application to Elucidating the Neuropharmacology of Amphetamines 431Craig R. Rush, Andrea R. Vansickel, and William W. StoopsA. Introduction 432B. Methodological Issues to Consider when Designing and Conducting a Human Drug Discrimination Experiment 433C. Using Human Drug Discrimination to Elucidate the Neuropharmacology of Amphetamines 444D. The Future of Human Drug Discrimination 44915. Nicotine Discrimination in Humans 463Kenneth A. PerkinsA. Introduction 464B. Basic Methods of Nicotine Discrimination Research in Humans 465C. Basic Parameters of Nicotine Discrimination 468D. Individual Differences and Moderators of Nicotine Discrimination 473E. Conclusions 47716. Drug Discrimination: A Perspective 483The late Francis C. ColpaertA. State Dependence and Drug Discrimination 484B. Drug Discrimination in Receptor Pharmacology 484C. Drug Discrimination and Subjective Drug Effects 485D. New Concepts of Opiate Tolerance, Signal Processing, Pain, and Analgesia 486E. Drug Discrimination: An Elementary Particle of Behavior and More 488F. When Dependent Variables Chose Their Pharmacology 491G. Two Further Mysteries 491H. Epilogue 492Index 497