Pharmacology of Ganglionic Transmission

535 Pages·1980·14.61 MB·English

by  D. A. Kharkevich (auth.), Professor Dr. Dimitry A. Kharkevich (eds.)

Handbook of
Experimental Pharmacology
Continuation of Handbuch der experimentellen Pharmakologie
Vol. 53
Editorial Board
G.V. R. Born, Cambridge . A. Farah, Rensselaer, New York
H. Herken, Berlin· A. D. Welch, Memphis, Tennessee
Advisory Board
S. Ebashi . E. G. Erdos· V. Erspamer . U. S. vo.n Euler· W. S. Feldberg
G. B. Koelle· O. Krayer . M. Rocha e Silva· J. R. Vane· P. G. Waser
W. Wilbrandt
Pharmacology of
Ganglionic Transmission
Contributors
D. M. Aviado . D. A. Brown· A. A. Bunatian· E. V Erina
L. Gyermek· WE. Haefely ~ D. A. Kharkevich
G. I. Klingman· J. D. Klingman· D. F. J. Mason
A. V Meshcherj akov . A. Nistri . D. T. Organisciak
1. P. Quilliam . V 1. Skok . V. TrCka . R. L. Volle
Editor
D. A. Kharkevich
Springer-Verlag Berlin Heidelberg New York 1980
Professor Dr. DIMITRY A. KHARKEVICH, Department of Pharmacology, First Medical
Institute, 2/6, B. Pirogovskaja St., USSR Moscow, 119435
With 72 Figures
ISBN-13: 978-3-642-67399-3 e-ISBN-13: 978-3-642-67397-9
DOl: 10.1007/978-3-642-67397-9
Library of Congress Cataloging in Publication Data. Main entry under title: Pharmacology of ganglionic transmission.
(Handbook of experimental pharmacology; v. 53) I. Ganglionic blocking agents. 2. Ganglia, Autonomic. 3. Neural
transmission. I. Aviado, Domingo M. II. Kharkevich, Dimitry Aleksandrovich. III. Series: Handbuch der ex peri men-
tellen Pharmakologie: New Series; v. 53. QP905.H3 vol. 53 [RM323J. 615'.1'08s. [615'.78] 79-9406.
This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned
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Softcover reprint of the hardcover I st edition 1980
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Contents
Introduction. D.A. KHARKEVICH. Withl Figure.
CHAPTER 1
Ganglionic Transmission: Morphology and Physiology. V.1. SKOK.
With 11 Figures
A. Pathways in the Autonomic Ganglia. 9
I. Extramural Ganglia . . . . . 9
II. Intramural Ganglia. . . . . . 10
III. Quantitative Relationship Between Preganglionic Fibres and Neuro-
nes of the Ganglion. . . . . . . . . . . . . . . . . . . 11
IV. Morphology of Neurones in the Ganglia. . . . . . . . . . 12
V. Embryogenesis and Development of Neurones in the Ganglia. 15
B. Synaptic Transmission in Autonomic Ganglia. . . . . . . . 16
I. Properties of Preganglionic Nerve Terminals. . . . . . . . 16
II. Acetylcholine as Excitatory Transmitter in the Ganglia. . . 16
III. Release of Acetylcholine From Preganglionic Nerve Terminals 17
IV. Nicotonic Cholinergic Transmission . . . . . . . . . . 18
V. Electrical Transmission. . . . . . . . . . . . . . . . 20
VI. Generation of Postsynaptic Spike. After-Hyperpolarization. 21
VII. Muscarinic Cholinergic and Adrenergic Transmissions. . 22
VIII. Role of Catecholamines in Transmission Through the Ganglia . 26
IX. Other Chemoceptive Sites in the Ganglion Neurones . 26
X. Inhibition in the Ganglia. . . 26
XI. Natural Activity ofthe Ganglia. 27
C. Summary. 29
References. . . . . . . . . . . . . . 30
CHAPTER 2
Ganglionic Metabolism. J.D. KLINGMAN, D. T. ORGANISCIAK, and
G.1. KLINGMAN. With 1 Figure
A. Carbohydrate Metabolism . . . . 41
B. Stimulation. . . . . . . . . . . 44
C. Nonglucose Metabolites Substrates 45
VI Contents
D. Lipids ............. . 47
E. Amino Acids . . . . . . . . . . . 52
F. Uptake and Efflux of Amino Acids. 54
G. RNA Protein . 56
H. Protein 57
References. . . . 57
CHAPTER 3
Methods for the Examination of Ganglion-Blocking Activity. L. GYERMEK.
With 16 Figures
A. Introduction . . . . . . . . . . . . . . . . . . . . . . . . 63
B. General Physiological and Pharmacological Aspects of the Evaluation of
Ganglion-Blocking Agents . . . . . 63
C. Pharmacological Methods . . . . . . . . . . . . . 65
I. In vivo and in situ Preparations. . . . . . . . . 65
1. Preparation of Superior Cervical Ganglia of Cat. 65
2. Other Sympathetic Ganglion Preparations. . . 78
3. Parasympathetic Ganglion Preparations (in vivo and in situ) . 83
4. Comparative Sensitivity of Sympathetic and Parasympathetic
Ganglia to Ganglionic Blockade. . . . . . . . . . . . .. 86
. II. Isolated Organ and Isolated Ganglion Preparations. . . . . .. 88
1. Isolated Smooth-Muscle Preparations of Gastrointestinal Tract 88
2. Other Isolated Organ Preparations. . . . . . . . . . .. 93
3. Isolated (Excised) Ganglion Preparations. . . . . . . . .. 96
D. Preparations Other Than Autonomic Ganglia Used for Evaluation of
Ganglion-Blocking Agents. . . . . . . . . . . . . . . . . . . . . 11)0
I. Preparations of Adrenal Gland and Adrenal Medulla . . . . . . . 100
II. Preparations Using the Response of Chemoreceptors of Carotid and
Aortic Bodies. . . . . . . . . . . . . . . . . . 10 1
III. Other Preparations . . . . . . . . . . . . . . . 102
IV. Antagonism Against the CNS Effects of Nicotine. . 102
1. Nicotine Convulsions and Toxicity. . 103
2. Behavioural Effects of Nicotine. . . . . . . . . 103
E. Screening for Ganglion-Blocking Activity. . . . . . . . 103
I. Blood Pressure Responses in Anaesthetised Animals . . 104
II. Mouse Pupil Mydriasis Test. . . . . . . . . . . . . 104
F. Evaluation of Non-Nicotinic Ganglion-Blocking Agents. . 105
G. Methods for the Determination of Absorption, Distribution, and Excretion
of Ganglion-Blocking Agents. . . . . . . . . . . . . . . . . . . . 106
H. Clinical Testing of Ganglion-Blocking Agents. . . . . . . . . . . . . 107
1. Critical Appraisal of the Experimental Methods Used in the Evaluation of
Ganglion-Blocking Agents . 108
K. Conclusions . 110
References. . . . . . . . . . 111
Contents VII
CHAPTER 4a
Relationship Between Chemical Structure and Ganglion-Blocking Activity.
a) Quaternary Ammonium Compounds.V. TRCKA. With 1 Figure
A. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . 123
B. Structure-Activity Relationships in Different Structural Types of Quaternary
Ganglion-Blocking Agents . . . . . . . . . . . . 126
I. Mono-Quaternary Ammonium Derivatives. . . . 126
1. Aliphatic Quaternary Ammonium Derivatives . 126
2. Heterocyclic Mono-Quaternary Derivatives. . 135
II. Bis-Quaternary Derivatives . . . . . . . . . . 136
1. Symmetrical Polymethylene Bis-Trialkylammonium Derivatives 136
2. Symmetrical Polymethylene-Bis-Quaternary Cyclic Compounds 139
3. Modifications of the Polymethylene Chain . 141
4. Asymmetrical Bis-Quaternary Compounds. . 141
5. Phosphonium and Sulphonium Derivatives. 145
C. Conclusions . . . . . . . . . . . . . . 150
1. Mono-Quaternary Compounds. . . . . 150
2. Symmetrical Bis-Quaternary Compounds. 150
References. . . . . . . . . . . . . . . . . 151
CHAPTER 4b
Relationship Between Chemical Structure and Ganglion-Blocking Activity.
b) Tertiary and Secondary Amines. V. TRCKA
A. Introduction . . . . . . . . . . . . . . . . . . . . . . . . 155
B. Structure-Activity Relationships in Different Structural Types of Non-
Quaternary Ganglion-Blocking Agents . 158
I. Substituted Aminoalkyl Derivatives . 158
II. Alicyclic Amines. . . . . . . . . . 166
III. Derivatives of 3-Aminoisocamphane . 166
IV. Piperidine Derivatives and Other N-Heterocyclic Compounds. 169
C. Conclusions 177
References. . . . . . . . . . . . . . . . . . . . . . . . . . . 182
CHAPTER 5
Locus and Mechanism of Action of Ganglion-Blocking Agents. D. A. BROWN.
With 7 Figures
A. Introduction . . . . . . . . . . . . . . . . . . 185
B. Competitive Blocking Agents. . . . . . . . . . . 185
I. Effects on the Transmission of Single Impulses . 185
VIII Contents
II. Presynaptic Effects. . . 187
1. Acetylcholine Release 187
2. Choline Uptake . . 188
3. Acetylcholine Synthesis 188
4. Electrical Responses of Preganglionic Nerves and Their Terminals. 189
5. Post-Tetanic Potentiation (PTP). . . 190
6. Repetitive Stimulation. . . . . . . 190
7. Presynaptic Acetylcholine Receptors. 191
8. Conclusions . . . . 192
III. Postsynaptic Effects . . . . . . . 193
1. Neuronal Excitability . . . . . 193
2. Action on Nicotinic Receptors. 194
3. Action on Skeletal Muscle Receptors . 200
4. Action on Muscarinic Receptors. . . 200
5. Action of Tetraethylammonium (TEA) . 201
C. Depolarising Agents. . . 204
I. Depolarisation Block . . . . 205
1. Theory ........ . 205
2. Experimental Observations. 206
II. Dissociation of Depolarisation and Block. 211
1. Off-Set Rates in vivo . . . . . 211
2. Postactivation Hyperpolarisation . . . 212
3. Desensitisation. . . . . . . . . . . 214
4. Differential Sites of Depolarisation and Transmission Block? . 215
5. Presynaptic Effects? . . . . . . . . . . . . . 217
6. Conclusions . . . . . . . . . . . . . . . . . 218
D. Intraganglionic Distribution of Ganglion-Blocking Drugs. 219
I. Non-Quaternary Agents . . . . . . . . . . . 219
1. Active Form of Non-Quaternary Compounds 220
II. Quaternary Ammonium Compounds. 221
1. Diffusion . . . . . . . . . 221
2. Receptor-Linked Penetration. 221
3. Carrier-Mediated Entry 222
Addendum 223
References. 226
CHAPTER 6
Action of Ganglion-Blocking Agents on the Cardiovascular System. D. M. AVIADO
A. Introduction . . . . . . . . . . . . . . . . . . . . . . 237
B. Hypotensive Action . . . . . . . . . . . . . . . . . . . 237
I. Cardiovascular Reflexes and the Central Nervous System 238
II. Circulating Humoral Agents and Injected Drugs. 238
C. Cardiac Function. . . . . . . . 239
I. Cardiac Output. . . . . . . 239
1. Decreased Cardiac Output . 239
2. Increased Cardiac Output . 239
Contents IX
II. Coronary Vascular Resistance 241
D. Systemic Vascular Beds . 241
I. Cerebral Circulation. . 242
II. Renal Circulation . . . 242
III. Pulmonary Circulation. 245
IV. Splanchnic Circulation. 247
V. Limb Circulation 247
E. Conclusions 248
References. . . . . . . 249
CHAPTER 7
Action of Ganglion-Blocking Agents on the Gastrointestinal Tract.
D. F. 1. MASON
A. Introduction.. . . . . . . . . . . 255
B. Salivary Secretion. . . . . . . . 256
C. Oesophagus and Cardiac Sphincter. 256
D. Gastric Motility. . . 257
E. Gastric Secretion . . 258
F. Pancreatic Secretion. 259
G. Small Intestine 259
H. Colon. 261
References. . 263
CHAPTER 8
Absorption, Distribution, Fate, and Excretion of Ganglion-Blocking Compounds.
D.F.l.MASON.
A. Introduction . . . 267
B. Onium Compounds 267
I. Absorption. 267
II. Distribution . 269
III. Excretion. . . 271
C. Secondary and Tertiary Amines . 272
I. Absorption. 272
II. Distribution 273
III. Excretion. 275
References. . . . . 276
CHAPTER 9
Nicotinic Ganglion-Stimulating Agents. R. L. VOLLE. With 12 Figures
A. Introduction . . . . . . . . . . . . . . . . . . . 281
B. Pharmacological Ambiguities of Ganglionic Receptors. . . . . 282
x Contents
C. Postj unctional Responses to Acetylcholine and Nicotinic Agents. 284
I. The Acetylcholine Potential ..... . 284
II. Surface or Demarcation Potentials. . . . 287
D. Blockade of Transmission by Nicotinic Drugs. 289
I. Depolarisation Blockade. . . . . . . . 289
II. Prolonged Ganglionic Blockade. . . . . 294
III. Postexcitatory Ganglionic Hyperpolarisation 297
IV. Presynaptic Nerve Terminals 300
E. Denervated Ganglia . 304
F. Conclusions 306
References. . . . . . . 307
CHAPTER 10
Non-Nicotinic Chemical Stimulation of Autonomic Ganglia. W. E. HAEFELY.
With 3 Figures
A. Introduction 313
B. Muscarinic Ganglion Stimulants 315
I. General Information. . 315
1. Acetylcholine (ACh) . . 315
2. Muscarine . . . . . . 322
3. Methacholine (Acetyl-,B-Methylcholine) . 323
4. Pilocarpine. . . . . . . . . . 325
5. Carbachol (Carbaminoylcholine) . 327
6. Arecoline. . . . . . . . . . . 328
7. Choline .......... . 328
8. Oxotremorine [1-(2-oxopyrrolidino)-4-pyrrolidino butyne-2] . 328
9. Furtrethonium (Furfuryltrimethylammonium) and Aceclidine . 329
10. 4-( m-Chlorophenylcarbamoyloxy)-2-B utyny 1-Trimethyl-
ammonium Chloride (McN-A-343) . . . . . . . . . . . . 329
11. n-Benzyl-3-Pyrrolidyl Acetate Methobromide (AHR-602) . 132
12. Quaternary Amino-Acid Esters. . . . . . . . . . . 333
13. Benzyltrimethylammonium and Pyridylmethyltrimethyl-
ammonium ................... . 333
14. Cholinesterase Inhibitors . . . . . . . . . . . . . . 333
II. Possible Involvement of a Second Messenger in Muscarinic Excitation
of Autonomic Ganglia. . . . . . . . . . . . . . . . 335
C. 5-Hydroxytryptamine (5-HT) and Related Indolealkylamines . 336
D. Histamine . . . . 339
E. Polypeptides . . . 341
I. Angiotensin II 341
II. Bradykinin. . 343
III. Various Peptides 344
1. Posterior Pituitary Hormones 344
2. Eledoisin and Physalaemin . 344
3. Substance P . . . . . . . . 344
Contents XI
F. Cardiac Glycosides 344
G. Veratrum Alkaloids 346
H. Batrachotoxin . . 347
J. Inorganic Cations. 347
I. Potassium 347
II. Caesium 348
III. Barium 349
IV. Calcium 349
K. Conclusions 350
References. . . · 351
CHAPTER 11
Ganglion Activity of Centrally Acting ~ eurotropic Agents.
A. NISTRI and J. P. QUILLIAM. With 1 Figure
A. Introduction . . . . 359
B. Methods ..... . 359
C. Volatile Anaesthetics. 362
D. Central Nervous System Depressants. 364
E. Neuroleptics . . . 368
I. Phenothiazines . . . 368
II. Thioxanthenes . . . .369
III. Rauwolfia Alkaloids. · 370
IV. Butyrophenones. . . .370
F. Antidepressants. . . . . · 371
I. Monoamine Oxidase Inhibitors (MAO I) . · 371
II. Tricyclic Antidepressants . · 371
G. Anti-Manic Drugs. . . . . . . . . . . .372
H. Narcotic Analgesics . . . . . . . . . . · 373
J. Central Nervous System-Stimulant Drugs. · 374
K. Tranquillisers. . . . · 377
L. Anticonvulsant Drugs .377
References. . . . . · 378
Note Added in Proof. . · 385
CHAPTER 12
Ganglionic Actions of Anticholinesterase Agents, Catecholamines, Neuro-
Muscular Blocking Agents, and Local Anaesthetics. R. L. VOLLE. With 10 Figures
A. Anticholinesterase Agents . . . . . . . 385
I. Effects on Acetylcholine Metabolism . 386
II. Nicotinic Ganglionic Transmission. . 389
III. Muscarinic Ganglionic Transmission. 390