Handbook of Psychopharmacology: Volume 14 Affective Disorders: Drug Actions in Animals and Man

388 Pages·1978·20.57 MB·English

by  Richard F. Squires (auth.)

of
Handbook
Psychopharmacology
Volume 14
Affective Disorders:
Drug Actions in Animals and Man
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 14
Affective Disorders:
Drug Actions in Animals and Man
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. 1. 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. - v. 13. Biology of Mood and Antianxiety
Drugs. - v. 14. Affective Disorders: Drug Actions in Animals and Man.!. Psycho
pharmacology. I. Iversen, Leslie Lars. n. Iversen, Susan D., 1940- In.
Snyder, Solomon H., 1938 [DNLM: 1. Psychopharmacology. QV77 H236]
RC483.1136 615'.78 75-6851
ISBN-13: 978-1-4613-4047-8 e-ISBN-13: 978-1-4613-4045-4
DOl: 10.1007/978-1-4613-4045-4
© 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 otherwis~, without written permission from the Publisher
CONTRIBUTORS
THOMAS P. DETRE, Department of Psychiatry, University of Pittsburgh School of
Medicine, and Western Psychiatric Institute and Clinic, Pittsburgh, Pennsyl
vanta
R. R. FIEVE, Lithium Clinic and Metabolic Research Unit, Columbia Presbyterian
Medical Center; Milhausen Depression Center Program, Atchley Pavilion;
Foundationfor Depression and Manic Depression, New York, NY.
SAMUEL GERSHON, Neuropsychopharmacology Research Unit, New York Univer
sity-Bellevue Hospital Center, New York, N.Y.
NELSON HOWARD HENDLER, Department oj Neurological Surgery and Depart
ment of Psychiatry and the Behavioral Sciences, The Johns Hopkins Univer
sity School oj Medicine, and The Johns Hopkins Hospital, Baltimore,
Maryland
DAVID J. KUPFER, Department of Psychiatry, University of Pittsburgh School oj
Medicine, and Western Psychiatric Institute and Clinic, Pittsburgh, Pennsyl
vanta
ROBERT A. MAXWELL, Department oj Pharmacology, Wellcome Research Labo
ratories, Burroughs Wellcome Co., Research Triangle Park, North Carolina
H. L. MELTZER, Lithium Clinic and Metabolic Research Unit Columbia Presby
terian Medical Center; Milhausen Depression Center Program, Atchley
Pavilion; Foundationfor Depression and Manic Depression, New York, N.Y.
DENNIS L. MURPHY, Clinical Neuropharmacology Branch, National Institute of
Mental Health, Bethesda, Maryland
BARON SHOPSIN, Neuropsychopharmacology Research Unit, New York Univer
sity-Bellevue Hospital Center, New York, N.Y.
RICHARD F. SQUIRES, Research Laboratories, A/S FERROSAN, Sydmarken 1-5,
DK-2860 Soeborg, Denmark
FRIDOLIN SULSER, Vanderbilt University School oj Medicine and Tennessee
Neuropsychiatric Institute, Nashville, Tennessee
HELEN L. WHITE, Department of Pharmacology, Wellcome Research Laborato
ries, Burroughs Wellcome Co., Research Triangle Park, North Carolina
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.1.
S.H.S.
VB
CONTENTS
CHAPTER 1
Monoamine Oxidase Inhibitors: Animal Pharmacology
RICHARD F. SQUIRES
1. Introduction .. . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.1. Localization..................................... 1
1.2. Function ....................................... 3
1.3. Mechanisms .................................... 3
2. Inhibition of 5-HT and Catecholamine Synthesis.. . . . . . . 5
3. Inhibition of Spontaneous Firing of 5-HT Neurons. . . . . . 6
4. Inhibitory Effects on Paradoxical Sleep and
Pontogeniculooccipital Waves ......................... 6
5. Effects on Growth and Development. . . . . . . . . . . . . . . . . . . 8
6. Inhibition of Ovulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
7. Effects on Lordosis .................................. 12
8. Effects on Male Copulatory Behavior .................. 12
9. 5-HT-Dependent Behavioral Syndromes ............... 14
9.1 MAOI plus Reserpine or Tetrabenazine. . . . . . . . . . . . 14
9.2. MAOI plus L-Tryptophan . . . . . . . . . . . . . . . . . . . . . . . . 15
9.3. MAOI plus 5-HTP .............................. 19
9.4. MAOI plus 5-HT-Uptake Inhibitor. . . . . . . . . . . . . . . . 20
10. Potentiation of Indoleamine Hallucinogens ............. 22
11. Tryptamine Potentiation ............................. 23
12. Potentiation of Phenethylamine Hallucinogens .......... 25
13. Hypotensive Effects. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
13.1. The False-Transmitter Hypothesis. . . . . . . . . .. . . . . . 27
13.2. Centrally Mediated Reduction of Blood Pressure. . . 28
14. Tyramine Potentiation ............................... 29
15. Interactions of the MAOIs with Reserpine and
Tetrabenazine.. . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . 30
16. Anticonvulsant Actions of MAOIs ..................... 31
ix
x CONTENTS
16.1. Electroshock and Metrazol Convulsions ........... 31
16.2. Audiogenic Seizures. . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
16.3. Other Types of Seizures ........................ 33
16.4. Conclusions ................................... 33
17. References ......................................... 33
CHAPTER 2
Monoamine Oxidase, Monoamine-Oxidase-Inhibiting Drugs, and
Human Behavior
DENNIS L. MURPHY
1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59
2. MAO-Inhibiting Drugs: Biologic, Physiologic, and
Behavioral Effects in Man ............................ 60
2.1. Monoamine Changes during MAO-Inhibitor
Administration to Man . . . . . . . . . . . . . . . . . . . . . . . . . . . 60
2.2. Physiological Changes during MAO-Inhibitor
Treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
2.3. Behavioral Changes during MAO-Inhibitor
Administration to Man . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
3. Monoamine Oxidase in Human Brain and Other Tissues. 63
4. Human Platelet Monoamine Oxidase .................. 65
4.1. Characteristics of Human Platelet Monoamine
Oxidase........................................ 65
4.2. Genetic Basis for Individual Differences in Platelet
MAO Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66
4.3. Factors Influencing Platelet MAO Activity. . . . . . . . . . 67
4.4. Drug Effects on Platelet MAO Activity . . . . . . . . . . . . . 70
4.5. Associations between Platelet MAO Activity and
Various Human Disorders. . . . . . . . . . . . . . . . . . . . . . . . 71
5. Possible Association between Platelet MAO Activity and
General Personality and Behavioral Factors. . . . . . . . . . . . . 75
6. References ......................................... 77
CHAPTER 3
Tricyclic and Monoamine Oxidase Inhibitor Antidepressants:
Structure-Activity Relationships
ROBERT A. MAXWELL and HELEN L. WHITE
1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83
1.1. Background .................................... 83
1.2. Purposes of this Review and a Limitation. . . . . . . . . . . 84
CONTENTS xi
2. Tricyclic and Related Compounds......... ............ 85
2.1. Neuronal Membrane Mechanisms for the Uptake of
Biogenic Amines ................................ 85
2.2. Inhibition of Norepinephrine Uptake. . . . . . . . . . . . . . 89
2.3. Inhibition of Catecholamine Uptake into
Dopaminergic Neurons....... .............. ..... 98
2.4. Inhibition of Serotonin Uptake. . . . . . . . . . . . . .. . . . . . 100
2.5. Relationship between Inhibition of the Uptake of
Biogenic Amines and Antidepressant Activity In Vivo:
Influence of Structural Modifications .............. 107
3. Monoamine Oxidase Inhibitors. . .. . . . . . . . . .. . . . .. . . .. . 112
3.1. The Active Site of Monoamine Oxidase. . . .. . . . . . . . 113
3.2. Structure-Activity Relationships among Substrates of
Monoamine Oxidase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114
3.3. Multiple Substrate-Binding Sites. . . . . . . . . . . . . . . . . . . 116
3.4. General Structural Requirements for Monoamine
Oxidase Inhibition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119
3.5. Structure-Activity Relationships among Inhibitors of
Monoamine Oxidase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121
4. MAOIs as Inhibitors of the Uptake of Biogenic Amines
and Tricyclic Compounds as Inhibitors of Monoamine
Oxidase ............................................ 135
4.1. MAOIs as Inhibitors of Amine Uptake. . . . . . . . . . . . . 135
4.2. Tricyclic Compounds as MAOIs . . . . . . . . . . . . . . . . . . . 137
5. Summary and Perspective ............................ 139
6. References ......................................... 145
CHAPTER 4
Tricyclic Antidepressants: Animal Pharmacology (Biochemical and
Metabolic Aspects)
FRIDOLIN SULSER
1. Introduction........................................ 157
2. Pharmacologic Test Procedures Predicting Clinical
Antidepressant Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 158
2.1. Potentiation of Exogenous and Endogenous
Catecholamines at Peripheral Adrenergic Receptor
Sites ................... '" .. . . . . . . . . . .. . .. . . .. . 160
2.2. Potentiation of Various Central Effects Elicited by
Amphetamine-like Drugs. . . . . . . . . . . . . . . .. . . .. . . . . 161
2.3. Antagonism of Guanethidine-Induced Catecholamine
Depletion and Adrenergic Neuron Blockade. . . . . . . . 162