Neuropoisons: Their Pathophysiological Actions

368 Pages·1995·8.656 MB·English

by  André de Vries, Eleanor Condrea (auth.), Lance L. Simpson (eds.)

NEUROPOISONS
THEIR PATHOPHYSIOLOGICAL ACTIONS
Volume 1-Poisons of Animal Origin
CONTRIBUTORS
Edward Barry Adams Department of Medicine, University of Natal,
Congel/a, Durban, South Africa.
Eleanor Condrea Department of Biochemistry, Tel-Aviv University
Medical School, and Rogoff-WeI/come Medical
Research Institute, Beilinson Hospital, Petah
Tikva, Israel.
D. R. Curtis Department of Physiology, Australian National
University, Canberra, Australia.
Wolf-Dietrich Dettbarn Department of Pharmacology, Vanderbilt University
School of Medicine, Nashvil/e, Tennessee, U~S.A.
Andre de Vries Department of Medicine, Tel-Aviv University Medical
School, and Rogoff-WeI/come Medical Research
Institute, Beilinson Hospital, Petah Tikva, Israel.
Daniel B. Drachman Department of Neurology, The Johns Hopkins University
School of Medicine and Hospital, Baltimore, Maryland,
U.S.A.
Peter W. Gage School of Physiology, University of New South Wales,
Kensington, New South Wales, Australia.
M. Glenn Koenig Department of Medicine, Vanderbilt University School
of Medicine, Nashville, Tennessee, U.S.A.
C. Y. Lee Pharmacological Institute, Col/ege of Medicine,
National Taiwan University, Taipei, Taiwan, China.
Yasumi Ogura Department of Pharmacology, Faculty of Dentistry,
Tohoku University, Sendai, Japan.
Philip Rosenberg Division of Pharmacology, School of Pharmacy and
Pharmacy Research Institute, The University of
Connecticut, Storrs, Connecticut, U.S.A.
Edward J. Schantz Biological Science Laboratories, Fort Detrick,
Frederick, Maryland, U.S.A.
Michael F. Sheff Ayer Laboratory, Pennsylvania Hospital, Philadelphia,
Pennsylvania, U.S.A.
Lance L. Simpson Laboratory of Chemical Biodynamics, University of
California, Berkeley, California, and Division of
Neuroscience, New York State Psychiatric Institute,
New York, New York, U.S.A.
Anthony T. Tu Department of Biochemistry, Colorado State University,
Fort Collins, Colorado, U.S.A.
James A. Vick Department of Pharmacology, Walter Reed Army Institute
of Research, Walter Reed Army Medical Center,
Washington, D.C., U.S.A.
Sumner I. Zacks Department of Pathology, University of Pennsylvania
School of Medicine, and Ayer Laboratory, Pennsylvania
Hospital, Philadelphia, Pennsylvania, U.S.A.
NEUROPOISONS
THEIR PATHOPHYSIOLOGICAL ACTIONS
Volume 1- Poisons of Animal Origin
Edited by Lance L. Simpson
Laboratory of Chemical Biodynamics
University of California
Berkeley, California
and
Division of Neuroscience
New York State Psychiatric Institute
New York, New York
9:>
PLENUM PRESS • NEW YORK-LONDON • 1971
Library of Congress Catalog Card Number 76-128511
ISBN-13: 978-1-4684-2942-8 e-ISBN-13: 978-1-4684-2940-4
DOl: 10.1007/978-1-4684-2940-4
© 1971 Plenum Press, New York
Softcover reprint of the hardcover 1s t edition 1971
A Division of Plenum Publishing Corporation
227 West 17th Street, New York, N.Y. 10011
United Kingdom edition published by Plenum Press, London
A Division of Plenum Publishing Company, Ltd.
Donington House, 30 Norfolk Street, London W.C. 2, England
All rights reserved
No part of this publication may be reproduced in any form
without written permission from the publisher
Preface
Poisons are topics of multidisciplinary concern. The clinician and the
pathologist are sensitive to instances of human poisoning. The laboratory
researcher, whether pharmacologist, physiologist, or biochemist, is oriented
toward molecular modes of poison action. Both clinician and researcher
are eager to learn of poisons that can be used as therapeutic agents or
methodological tools.
This volume is an attempt to underscore the multidisciplinary charac
ter of neuropoisons. Six poisons of animal origin which are receiving
considerable clinical and research attention are discussed. Each poison is
presented first as a clinical entity, then as a topic of investigative research,
and finally as an agent useful to the study of nerve function.
Because no single volume on neuropoisons can be exhaustive, an
attempt at balance is offered as compensation. Two snake venoms, two
marine poisons, and two bacterial toxins are presented in detail. In the
sequel to this volume, attention will be focused on representative neuro
poisons of plant origin.
Lance L. Simpson
New York City
September, 1970
v
Contents
Chapter 1
Clinical Aspects of Elapid Bite...................................................... 1
by Andre de Vries and Eleanor Condrea
I. Introduction ............................................................... 1
II. Elapidae . ........ .. .......... .. ....... ... ... .... .. ... .. ....... ... ...... ...... 1
A. Classification...... ......... ... .. . .. ....... ..... .. ..... ..... ....... ... 1
B. Geographic Distribution .......................................... 2
C. Venom Toxicity ...................................................... 2
D. Venom Yield ......................................................... 3
E. Epidemiology......................................................... 3
III. Symptomatology of Elapid Bite....................................... 6
A. General Characteristics............................................. 6
B. Local Poisoning...................................................... 7
C. Systemic Poisoning................................................... 8
IV. Treatment. .................................................................... 10
A. Indigenous and Chemical Treatment.. ......................... 10
B. First Aid ............................................................... 11
C. Antivenins ............................................................ 12
D. Cryotherapy ......................................................... 14
E. Tracheostomy and Artificial Respiration ........................ 15
F. Antibiotics and Tetanus Antitoxin .............................. 15
G. Corticosteroids, Antihistaminics, and Other Drugs ......... 16
H. Treatment of Ophthalmia.......................................... 17
V. References .................................................................. 17
Chapter 2
Mode of Action of Cobra Venom and Its Purified Toxins ..................... 21
by C. Y. Lee
I. Introduction ............................................................... 21
II. Chemistry of Cobra Venom ............................................. 23
A. Neurotoxins ......................................................... 23
B. Cardiotoxin, Cobramines, DLF, Toxin y, and Cytotoxin ... 27
C. Enzymes. ..... .......... ..... ..... ....... ... ......... ......... ......... 30
D. Nonproteins ......................................................... 33
vii
viii Contents
III. Pharmacological Actions of Cobra Venom ........................... 36
A. Toxicity, Symptoms Produced in Animals, and Cause of
Death ............................................................... 36
B. Absorption, Distribution, and Fate .............................. 38
C. Actions on Neuromuscular Junction, Skeletal Muscle, and
Nerve ............................................................... 39
D. Action on Smooth Muscle .......................................... 45
E. Action on Sympathetic Ganglionic Transmission............ 46
F. Action on the Cardiovascular System ........................... 47
G. Local Action ......................................................... 49
H. Actions on the Central Nervous System........................ 50
I. Actions on Blood ................................................... 52
J. Biochemical Effects ................................................... 54
K. Cytotoxic Effects...................................................... 58
IV. Concluding Remarks ...................................................... 60
V. References .................................................................. 63
Chapter 3
Symptomatology of Experimental and Clinical Crotalid Envenomation ... 71
by James A. Vick
I. The Rattlesnake ............................................................ 71
II. Rattlesnake Venom Potency............................................. 73
A. Mouse .................................................................. 73
B. Dog ..................................................................... 75
C. Monkey ............................................................... 75
D. Averaged Potency ................................................... 75
III. Physiological Effects of Venom .......................................... 76
A. Effects of Venom on Cortical Electrical Activity ............ 77
B. Effects of Venom on Plasma Factors .............................. 79
C. Effects of Actual Snake Bite....................................... 81
IV. Treatment of Snake Bite ................................................ 84
V. Concluding Remarks...................................................... 85
VI. References ............... ... ... ... ... ... ... ............... ........ .......... 86
Chapter 4
The Mechanism of Snake Venom Actions-Rattlesnakes and Other
Crotalids .. .......... ...... .. . ...... ... ... ... ..... .......................... . .. ........ 87
by Anthony T. Tu
I. Introduction .............. ................................................. 87
A. Snakes in Family Crotalidae ....................................... 87
Contents ix
B. Components of Snake Venoms .................................... 88
II. Action of Snake Venoms ................................................ 89
A. Local Actions......................................................... 89
B. Systemic Action...................................................... 92
C. Autopharmacological Effects .................................... l 04
D. Lethal Action of Snake Venoms ................................. 105
III. References .................................................................. 106
Chapter 5
The Use of Snake Venoms as Pharmacological Tools in Studying Nerve
Activity ................................................................................. 111
by Philip Rosenberg
I. Introduction ............................................................... 111
II. Development and Differentiation of the Nervous System ......... 112
III. Neuronal Degeneration and Demyelination ........................ 113
A. Immunosympathectomy by Antibodies to Nerve Growth
Factor ............................................................... 113
B. Neuropathological Changes Induced by Venoms ............ 113
IV. Axonal Conduction ...................................................... 114
A. Use of Venoms as Chemical'Dissectors ........................ 114
B. Effects of Cholinergic Agents on Axonal Conduction ......... 115
C. The Acetylcholine Receptor .................................... 119
D. Hyperexcitability ................................................... 120
V. Membrane Permeability ................................................ 120
A. Increased Permeability Induced by Venoms .................. 120
B. Structural Alterations Associated with Increased Per-
meability ............................................................ 124
VI. Phospholipid Function in Nerve ....................................... 125
A. Component of Venom Responsible for Effects on Axon ... 125
B. Mechanism of Phospholipase A Effects on Conduction and
Permeability ......................................................... 126
C. Maintenance of Conduction and Permeability in Presence
of Phospholipid Splitting ....................................... 127
VII. Neuronal Metabolism ................................................... 129
A. Function and Structure of Mitochondria ........................ 129
B. Acetylcholine-Synthesis, Storage, Release, and Hydrolysis131
VIII. Conclusions .................................................................. 133
IX. References .................................................................. 134
x Contents
Chapter 6
Fugu (Puffer-Fish) Poisoning and the Pharmacology of Crystalline
Tetrodotoxin in Poisoning ......................................................... 139
by Yasumi Ogura
I. Introduction ............................................................... 139
II. Actual Conditions and Statistical Survey of Fugu Poisoning ...... 141
A. Varieties ofFugu ...................................................... 141
B. Localization ............................................................ 141
C. Influence of Season ................................................... 141
D. Statistical Survey ................................................... 141
E. Differences between Fugu Poisoning and Ciguatera ......... 143
III. Clinical Symptoms and Treatment of Fugu Intoxication ......... 144
IV. Pharmacological Actions Underlying Clinical Symptons ......... 145
A. Emetic Action ......................................................... 145
B. Circulation ............................................................ 146
C. Respiration ............................................................ 147
D. Excitable Cells ...................................................... 148
E. N onexcitable Cells ................................................... 149
F. Biochemical Aspects ................................................ 151
G. Relationship between Chemical Structure and Pharmacolog-
ical Action ......................................................... 151
H. Absorption, Distribution, and Excretion ........................ 153
V. Legislative Control for Preventing Fugu Poisoning in Japan ... 154
VI. Tested Clinical Use of Crystalline Tetrodotoxin ..................... 155
VII. References .................................................................. 156
Chapter 7
Paralytic Shellfish Poisoning and Saxitoxin .................................... 159
by Edward J. Schantz
I. Occurrence and Distribution of Paralytic Shellfish Poisoning ... 159
II. Shellfish Poisoning as a Public Health Problem ..................... 162
III. Detection of Shellfish Poisoning ....................................... 163
IV. Isolation and Characterization of Shellfish Poisons ............... 164
V. References .................................................................. 167
Chapter 8
Mechanism of Action of Tetrodotoxin (TTX) and Saxitoxin (STX) ............ 169
by W olf-Dietrich Dettbarn
I. Introduction ............................................................... 169
II. The Nature of the Nerve Impulse ....................................... 169
III. Cellular Actions of TTX and STX .................................... 172
Contents xi
A. Peripheral Nerve ...................................................... 172
B. Skeletal Muscle ...................................................... 176
C. The Acetylcholine System .......................................... 177
D. Action of TTX and STX on Generator Potentials ............ 177
IV. Comparison of TTX and STX .......................................... 178
V. Mechanism of Action ...................................................... 179
A. The Active Form of TTX and STX .............................. 179
B. Structure-Activity Relationship ................................. 180
C. Possible Mechanism of Interaction ... : .......................... 182
D. The Interaction of TTX and STX with Calcium ............... 184
E. Model Systems ......................................................... 184
VI. Conclusion .................................................................. 185
VII. References .................................................................. 185
Chapter 9
Tetrodotoxin and Saxitoxin as Pharmacological Tools ........................... 187
by Peter W. Gage
I. Introduction . ~' ............................................................. 187
A. History .................................................................. 187
B. Chemistry ............................................................... 188
II. Cellular Effects ............................................................ 190
A. Properties of Excitable Membranes .............................. 190
B. Actions of Toxins ................................................... 191
III. Pharmacological Uses ................................................... 193
A. The Early Transient Channel .................................... 194
B. Synaptic Transmission ............................................. 195
C. Central Nervous System ............................................. 204
D. Generator Potentials ................................................ 206
E. Action Potentials Not Dependent on Sodium Ions ............ 208
F. General. ................................................................. 209
IV. Conclusion .................................................................. 210
V. References .................................................................. 211
Chapter 10
The Clinical Effects of Tetanus ...................................................... 213
by Edward Barry Adams
I. Tetanus: The World Problem .......................................... 213
II. Clinical Features ............................................................ 214
III. The Natural History of Tetanus ....................................... 216
IV. Complications ............................................................... 218
V. Causes of Death ............................................................ 219