Drugs of Abuse

428 Pages·1978·10.09 MB·English

by  Roy Pickens

of
Handbook
Psychopharmacology
Volume 12
Drugs of Abuse
of
Handbook
Psychopharmacology
SECTION I: BASIC NEUROPHARMACOLOGY
Volume 1 Biochemical Principles and Techniques in Neuropharmacology
Volume 2 Principles of Receptor Research
Volume 3 Biochemistry of Biogenic Amines
Volume 4 Amino Acid Neurotransmitters
Volume 5 Synaptic Modulators
Volume 6 Biogenic Amine Receptors
SECTION II: BEHAVIORAL PHARMACOLOGY IN ANIMALS
Volume 7 Principles of Behavioral Pharmacology
Volume 8 Drugs, Neurotransmitters, and Behavior
Volume 9 Chemical Pathways in the Brain
SECTION III: HUMAN PSYCHOPHARMACOLOGY
Volume 10 Neuroleptics and Schizophrenia
Volume 11 Stimulants
Volume 12 Drugs of Abuse
Volume 13 Biology of Mood and Antianxiety Drugs
Volume 14 Affective Disorders: Drug Actions in Animals and Man
Volume 12
Drugs of Abuse
Edited by
Leslie L. Iversen
Department of Pharmacology
University of Cambridge
Susan D. Iversen
Department of Psychology
University of Cambridge
and
Solomon H. Snyder
Departments of Pharmacology and Psychiatry
The Johns Hopkins University
School of Medicine
PLENUM PRESS • NEW YORK AND LONDON
Library of Congress Cataloging in Publication Data
Main entry under title:
Handbook of psychopharmacology.
Includes bibliographies and indexes.
CONTENTS: v.I. Biochemical principles and techniques in neuropharmacology.
-v. 2. Principles of receptor research. - v. 3. Biochemistry of biogenic amines. -
v. 4. Amino acid neurotransmitters. - v. 5. Synaptic modulators. - v. 6. Biogenic
amine receptors. - v. 7. Principles of behavioral pharmacology. - v. 8. Drugs,
Neurotransmitters, and Behavior. - v. 10. Neuroleptics and Schizophrenia. - v.
11. Stimulants. - v. 12. Drugs of Abuse. 1. Psychopharmacology. I. Iversen,
Leslie Lars. II. Iversen, Susan D., 1940· III. Snyder, Solomon H., 1938-
[DNLM: 1. Psychopharmacology. QV77 H236]
RC483.H36 615'.78 75-6851
ISBN 978-1-4684-3188-9 ISBN 978-1-4684-3186-5 (eBook)
DOl 10.1007/978-1-4684-3186-5
© 1978 Plenum Press, New York
Softcover reprint of the hardcover 1st edition 1978
A Division of Plenum Publishing Corporation
227 West 17th Street, New York, N.Y. 10011
All rights reserved
No part of this book may be reproduced, stored in a retrieval system, or transmitted,
in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission from the Publisher
CONTRIBUTORS
ARTHUR E. JACOBSON, Ml'dicinal Chemistry Section, Laboratory oj Chemistry,
National Institute of Arthritis, Metabolism, and Digestive Diseases, National
Institutl's lif Hl'alth, Bethesda, Maryland
REESE T. JONES, Langll'y Portl'r Neuropsychiatric Institute, University oj Califor
nia, San Francisco, California
PETER A. MANSKY, Dl'partment (if Psychiatry, Albert B. Chandler Medical
Center, University lif Kentucky, Lexington, Kentucky
RICHARD A. MEISCH, University oj Minnesota, Minneapolis, Minnesota
NANCY K. MELLO, Alcohol and Drug Abuse Research Center, Harvard Medical
School-McLean Hospital, Bl'lmont, Massachusetts
JACK H. MENDELSON, Alcohol and Drug Abuse Research Center, Harvard
Ml'dical School-McLean Hospital, Belmont, Massachusetts
ROGER A. NICOLL, Department of Pharmacology and Physiology, University oj
California, San Francisco, California
Roy PICKENS, University lif Minnesota, Minneapolis, Minnesota
R. DUANE SOFIA, Biological Resrarch, Walia((' Laboratorirs, Cranbury, New
jersey
TRAVIS THOMPSON, University (if Minnesota, Minneapolis, Minnesota
v
PREFACE
Underlying the design of the Handbook of Psychopharmacology is a prejudice
that the study of drug influences on the mind has advanced to a stage where
basic research and clinical application truly mesh. These later volumes of the
Handbook are structured according to this conception. In certain volumes,
groups of drugs are treated as classes with chapters ranging from basic
chemistry to clinical application. Other volumes are assembled around topic
areas such as anxiety or affective disorders. Thus, besides chapters on
individual drug classes, we have included essays addressing broad areas such
as "The Limbic-Hypothalamic-Pituitary-Adrenal System and Human Be
havior" and "Peptides and the Central Nervous System."
Surveying these diverse contributions, one comes away with a sentiment
that, far from being an "applied" science borrowing from fundamental brain
chemistry and physiology, psychopharmacology has instead provided basic
researchers with the tools and conceptual approaches which now are
advancing neurobiology to a central role in modern biology. Especially
gratifying is the sense that, while contributing to an understanding of how
the brain functions, psychopharmacology is a discipline whose fruits offer
genuine help to the mentally ill with promises of escalating benefits in the
future.
L.L.1.
S.D. I.
S.H.S.
VII
CONTENTS
CHAPTER 1
Drug Self-Administration: An Analysis of the Reinforcing
Effects of Drugs
Roy PICKENS, RICHARD A. MEISCH, and TRAVIS THOMPSON
1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . I
2. Methods of Self-Administration ....................... 3
3. Establishing Drugs as Reinforcers. . . . . . . . . . . . . . . . . . . . . . 4
4. Characteristics of Self-Administration .................. 7
4.1. Ethanol....................................... 8
4.2. Sedatives...................................... 10
4.3. Opiates ....................................... I I
4.4. Stimulants..................................... 13
4.5. Other Drug Classes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
5. Drugs Not Self-Administered ......................... 19
6. Factors Influencing Self-Administration ................ 20
6.1. Organismic.................................... 20
6.2. Past History ................................... 21
6.3. Motivational................................... 21
6.4. Stimulus Control ............................... 23
6.5. Reinforcement Schedules. . . . . . . . . . . . . . . . . . . . . . . . 24
7. Elimination of Self-Administration. . . . . . . . . . . . . . . . . . . . . 28
7.1. Punishment.................................... 29
7.2. Extinction..................................... 29
8. Conclusions......................................... 30
9. References ......................................... 31
CHAPTER 2
Analgesics and Their Antagonists: Structure-Activity Relationships
ARTHUR E. JACOBSON
I. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
2. Alkaloids Derived from Opium, and Their Derivatives 40
IX
x C()NT1~'lVTS
2.1. Substitutions on the Aromatic Ring (Ring A) . . . . . . . 41
2.2. Changes at the Allylic Alcohol Moiety (Ring C) . . . . . 44
2.3. Modifications Affecting the Shape of Morphine (B/C
Rings) . . . .. .. . . .. . . . . . . . . . . . .. . . .. ... . . . ... . .. . 47
2.4. Epoxide Ring Opening and the Effect of C-l 0 and
C-14 Hydroxyl Groups (Rings B and D) . . . . . . . . . . . 47
2.5. Substituents on the Nitrogen Atom ............... 48
3. Pethidines .............. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50
3.1. Prodines and Ketobemidones .................... 60
4. Methadones ........................................ 61
5. Miscellaneous Analgesics ............................. 63
6. Complex Morphine Derivatives: The "M" Series. . . . . . . . . 64
7. Morphinans ......................................... 66
8. Benzomorphans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67
9. Structure-Activity: Theory ........................... 78
9.1. Qualitative Theory ............................. 78
9.2. Quantitative Theory. . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
9.3. Conclusion .................................... 85
10. References ......................................... 85
CHAPTER 3
Opiates: Human Psychopharmacology
PETER A. MANSKY
1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95
2. Opiate Metabolism. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96
2.1. Introduction................................... 96
2.2. Absorption.................................... 96
2.3. Distribution.................................... 97
2.4. Metabolism and Excretion. . . . . . . . . . . . . . . . . . . . . . . 98
3. Behavioral and General Subjective Effects (Activating
Effects, Sedating Effects, and Somatic Effects) . . . . . . . . . . . 99
3.1. Introduction................................... 99
3.2. Observations in Former Addict Populations. . . . . . . . 100
3.3. Comparison of Effects in Nonaddict Populations ... 101
3.4. Effects on Sleep . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104
3.5. Methodological Considerations ................... 104
3.6. Behavioral Effects of Opiate Agonist-Antagonists. . . 113
4. Effects of Opiates on Mood. . . . . . . . . . . . . . . . . . . . . . . . . . . 113
4.1. Introduction................................... 113
4.2. Measurement of Mood Effects of Opiate Agonists
and Agonist-Antagonists ........................ 115
5. Pain and Analgesia .................................. 118
5.1. Pain Phenomenology ........................... 118
5.2. Psychological Factors Influencing Pain ............ 121
CONTENTS Xl
5.3. Pain Pathways--The Neuroanatomical and
Neurophysiological Aspects of the Processing of
Nociceptive Stimuli ............................. 129
5.4. Analgesia...................................... 135
5.5. Opiate Analgesia ............................... 137
6. Other Pharmacological Actions of Opiates .............. 141
6.1. Gastrointestinal Effects . . . . . . . . . . . . . . . . . . . . . . . . . . 141
6.2. Respiratory Effects ............................. 144
6.3. Cardiovascular Effects .......................... 146
6.4. Pupillary Effects. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147
6.5. Urinary Tract Effects. . . . . . . . . . . . . . . . . . . . . . . . . . . 148
6.6. Other Effects of Single-Dose Opiate Administration. 149
7. Chronic Administration of Opiates .................... 150
7.1. Phenomenology................................ 150
7.2. Tolerance..................................... 153
7.3. Dependence................................... 157
7.4. Tolerance and Dependence with Opiate Agonist-
Antagonists . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 166
7.5. Theories of Tolerance and Dependence. . . . . . . . . . . 167
8. Classification of Opiates from Human Studies. . . . . . . . . . . 170
9. References ......................................... 173
CHAPTER 4
Sedative-Hypnotics: Animal Pharmacology
ROGER A. NICOLL
1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 187
1.1. Definition..................................... 187
1.2. Nature of the Problem ... . . . . . . . . . . . . . . . . . . . . . . . 188
1.3. General Properties of CNS Depressants ........... 189
1.4. Site of Action ...... . . . . . . . . . . . . . . . . . . . . . . . . . . . . 190
2. Axons ............................................. 190
3. Synapses........................................... 191
3.1. General Effects on Transmission ................. 19 I
3.2. Presynaptic Effects ............................. 198
3.3. Effects on Transmitter Action. . . . . . . . . . . . . . . . . . . . 206
4. Postsynaptic Membranes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 I 5
4. I. Muscle and Invertebrate Neurons ................ 2 I;)
4.2. Vertebrate CNS ................................ 216
;). Correlation of Barbiturate Anesthesia \\'ith SIO\\'-Wave
Sleep .............................................. 2 1~)
6. Excitatory Actions of Barbiturates ..................... 220
7. Conclusions......................................... 223
8. References ......................................... 224