Pharmacology of Ganglionic Transmission

1 Ganglionic Transmission: Morphology and Physiology.- A. Pathways in the Autonomic Ganglia.- I. Extramural Ganglia.- II. Intramural Ganglia.- III. Quantitative Relationship Between Preganglionic Fibres and Neurones of the Ganglion.- IV. Morphology of Neurones in the Ganglia.- V. Embryogenesis and Development of Neurones in the Ganglia.- B. Synaptic Transmission in Autonomic Ganglia.- I. Properties of Preganglionic Nerve Terminals.- II. Acetylcholine as Excitatory Transmitter in the Ganglia.- III. Release of Acetylcholine From Preganglionic Nerve Terminals.- IV. Nicotonic Cholinergic Transmission.- V. Electrical Transmission.- VI. Generation of Postsynaptic Spike. After-Hyper polarization.- VII. Muscarinic Cholinergic and Adrenergic Transmissions.- VIII. Role of Catecholamines in Transmission Through the Ganglia.- IX. Other Chemoceptive Sites in the Ganglion Neurones.- X. Inhibition in the Ganglia.- XI. Natural Activity of the Ganglia.- C. Summary.- References.- 2 Ganglionic Metabolism.- A. Carbohydrate Metabolism.- B. Stimulation.- C. Nonglucose Metabolites Substrates.- D. Lipids.- E. Amino Acids.- F. Uptake and Efflux of Amino Acids.- G. RNA Protein.- H. Protein.- References.- 3 Methods for the Examination of Ganglion-Blocking Activity.- A. Introduction.- B. General Physiological and Pharmacological Aspects of the Evaluation of Ganglion-Blocking Agents.- C. Pharmacological Methods.- I. In vivo and in situ Preparations.- 1. Preparation of Superior Cervical Ganglia of Cat.- 2. Other Sympathetic Ganglion Preparations.- 3. Parasympathetic Ganglion Preparations (in vivo and in situ).- 4. Comparative Sensitivity of Sympathetic and Parasympathetic Ganglia to Ganglionic Blockade.- II. Isolated Organ and Isolated Ganglion Preparations.- 1. Isolated Smooth-Muscle Preparations of Gastrointestinal Tract.- 2. Other Isolated Organ Preparations.- 3. Isolated (Excised) Ganglion Preparations.- D. Preparations Other Than Autonomic Ganglia Used for Evaluation of Ganglion-Blocking Agents.- I. Preparations of Adrenal Gland and Adrenal Medulla.- II. Preparations Using the Response of Chemoreceptors of Carotid and Aortic Bodies.- III. Other Preparations.- IV. Antagonism Against the CNS Effects of Nicotine.- 1. Nicotine Convulsions and Toxicity.- 2. Behavioural Effects of Nicotine.- E. Screening for Ganglion-Blocking Activity.- I. Blood Pressure Responses in Anaesthetised Animals.- II. Mouse Pupil Mydriasis Test.- F. Evaluation of Non-Nicotinic Ganglion-Blocking Agents.- G. Methods for the Determination of Absorption, Distribution, and Excretion of Ganglion-Blocking Agents.- H. Clinical Testing of Ganglion-Blocking Agents.- J. Critical Appraisal of the Experimental Methods Used in the Evaluation of Ganglion-Blocking Agents.- K. Conclusions.- References.- 4a Relationship Between Chemical Structure and Ganglion-Blocking Activity. a) Quaternary Ammonium Compounds.- A. Introduction.- B. Structure-Activity Relationships in Different Structural Types of Quaternary Ganglion-Blocking Agents.- I. Mono-Quaternary Ammonium Derivatives.- 1. Aliphatic Quaternary Ammonium Derivatives.- 2. Heterocyclic Mono-Quaternary Derivatives.- II. Bis-Quaternary Derivatives.- 1. Symmetrical Polymethylene Bis-Trialkylammonium Derivatives.- 2. Symmetrical Polymethylene-Bis-Quaternary Cyclic Compounds.- 3. Modifications of the Polymethylene Chain.- 4. Asymmetrical Bis-Quaternary Compounds.- 5. Phosphonium and Sulphonium Derivatives.- C. Conclusions.- 1. Mono-Quaternary Compounds.- 2. Symmetrical Bis-Quaternary Compounds.- References.- 4b Relationship Between Chemical Structure and Ganglion-Blocking Activity. b) Tertiary and Secondary Amines.- A. Introduction.- B. Structure-Activity Relationships in Different Structural Types of Non-Quaternary Ganglion-Blocking Agents.- I. Substituted Aminoalkyl Derivatives.- II. Alicyclic Amines.- III. Derivatives of 3-Aminoisocamphane.- IV. Piperidine Derivatives and Other N-Heterocyclic Compounds.- C. Conclusions.- References.- 5 Locus and Mechanism of Action of Ganglion-Blocking Agents.- A. Introduction.- B. Competitive Blocking Agents.- I. Effects on the Transmission of Single Impulses.- II. Presynaptic Effects.- 1. Acetylcholine Release.- 2. Choline Uptake.- 3. Acetylcholine Synthesis.- 4. Electrical Responses of Preganglionic Nerves and Their Terminals.- 5. Post-Tetanic Potentiation (PTP).- 6. Repetitive Stimulation.- 7. Presynaptic Acetylcholine Receptors.- 8. Conclusions.- III. Postsynaptic Effects.- 1. Neuronal Excitability.- 2. Action on Nicotinic Receptors.- 3. Action on Skeletal Muscle Receptors.- 4. Action on Muscarinic Receptors.- 5. Action of Tetraethylammonium (TEA).- C. Depolarising Agents.- I. Depolarisation Block.- 1. Theory.- 2. Experimental Observations.- II. Dissociation of Depolarisation and Block.- 1. Off-Set Rates in vivo.- 2. Postactivation Hyperpolarisation.- 3. Desensitisation.- 4. Differential Sites of Depolarisation and Transmission Block?.- 5. Presynaptic Effects?.- 6. Conclusions.- D. Intraganglionic Distribution of Ganglion-Blocking Drugs.- I. Non-Quaternary Agents.- 1. Active Form of Non-Quaternary Compounds.- II. Quaternary Ammonium Compounds.- 1. Diffusion.- 2. Receptor-Linked Penetration.- 3. Carrier-Mediated Entry.- Addendum.- References.- 6 Action of Ganglion-Blocking Agents on the Cardiovascular System.- A. Introduction.- B. Hypotensive Action.- I. Cardiovascular Reflexes and the Central Nervous System.- II. Circulating Humoral Agents and Injected Drugs.- C. Cardiac Function.- I. Cardiac Output.- 1. Decreased Cardiac Output.- 2. Increased Cardiac Output.- II. Coronary Vascular Resistance.- D. Systemic Vascular Beds.- I. Cerebral Circulation.- II. Renal Circulation.- III. Pulmonary Circulation.- IV. Splanchnic Circulation.- V. Limb Circulation.- E. Conclusions.- References.- 7 Action of Ganglion-Blocking Agents on the Gastrointestinal Tract..- A. Introduction.- B. Salivary Secretion.- C. Oesophagus and Cardiac Sphincter.- D. Gastric Motility.- E. Gastric Secretion.- F. Pancreatic Secretion.- G. Small Intestine.- H. Colon.- References.- 8 Absorption, Distribution, Fate, and Excretion of Ganglion-Blocking Compounds..- A. Introduction.- B. Onium Compounds.- I. Absorption.- II. Distribution.- III. Excretion.- C. Secondary and Tertiary Amines.- I. Absorption.- II. Distribution.- III. Excretion.- References.- 9 Nicotinic Ganglion-Stimulating Agents.- A. Introduction.- B. Pharmacological Ambiguities of Ganglionic Receptors.- C. Postjunctional Responses to Acetylcholine and Nicotinic Agents.- I. The Acetylcholine Potential.- II. Surface or Demarcation Potentials.- D. Blockade of Transmission by Nicotinic Drugs.- I. Depolarisation Blockade.- II. Prolonged Ganglionic Blockade.- III. Postexcitatory Ganglionic Hyperpolarisation.- IV. Presynaptic Nerve Terminals.- E. Denervated Ganglia.- F. Conclusions.- References.- 10 Non-Nicotinic Chemical Stimulation of Autonomic Ganglia.- A. Introduction.- B. Muscarinic Ganglion Stimulants.- I. General Information.- 1. Acetylcholine (ACh).- 2. Muscarine.- 3. Methacholine(Acetyl-3b2-Methylcholine).- 4. Pilocarpine.- 5. Carbachol (Carbaminoylcholine).- 6. Arecoline.- 7. Choline.- 8. Oxotremorine [l-(2-oxopyrrolidino)-4-pyrrolidino butyne-2].- 9. Furtrethonium (Furfuryltrimethylammonium) and Aceclidine.- 10. 4-(m-Chlorophenylcarbamoyloxy)-2-Butynyl-Trimethyl-ammonium Chloride (McN-A-343).- 11. n-Benzyl-3-Pyrrolidyl Acetate Methobromide (AHR-602).- 12. Quaternary Amino-Acid Esters.- 13. Benzyltrimethylammonium and Pyridylmethyltrimethyl-ammonium.- 14. Cholinesterase Inhibitors.- II. Possible Involvement of a Second Messenger in Muscarinic Excitation of Autonomic Ganglia.- C. 5-Hydroxytryptamine (5-HT) and Related Indolealkylamines.- D. Histamine.- E. Polypeptides.- I. Angiotensin II.- II. Bradykinin.- III. Various Peptides.- 1. Posterior Pituitary Hormones.- 2. Eledoisin and Physalaemin.- 3. Substance P.- F. Cardiac Glycosides.- G. Veratrum Alkaloids.- H. Batrachotoxin.- J. Inorganic Cations.- I. Potassium.- II. Caesium.- III. Barium.- IV. Calcium.- K. Conclusions.- References.- 11 Ganglion Activity of Centrally Acting Neurotropic Agents..- A. Introduction.- B. Methods.- C. Volatile Anaesthetics.- D. Central Nervous System Depressants.- E. Neuroleptics.- I. Phenothiazines.- II. Thioxanthenes.- III. Rauwolfia Alkaloids.- IV. Butyrophenones.- F. Antidepressants.- I. Monoamine Oxidase Inhibitors (MAOI).- II. Tricyclic Antidepressants.- G. Anti-Manic Drugs.- H. Narcotic Analgesics.- J. Central Nervous System-Stimulant Drugs.- K. Tranquillisers.- L. Anticonvulsant Drugs.- References.- Note Added in Proof.- 12 Ganglionic Actions of Anticholinesterase Agents, Catecholamines, Neuro-Muscular Blocking Agents, and Local Anaesthetics.- A. Anticholinesterase Agents.- I. Effects on Acetylcholine Metabolism.- II. Nicotinic Ganglionic Transmission.- III. Muscarinic Ganglionic Transmission.- B. Catecholamines.- I. Catecholamines and the Slow Synaptic Inhibitory Potential.- II. Presynaptic Blockade by Catecholamines.- III. Catecholamines and Ganglionic Cyclic Nucleotides.- IV. Catecholamines as Modulators of Transmission.- C. Neuromuscular Blocking Agents.- D. Local Anaesthetics.- E. Conclusions.- References.- 13 Ganglionic Activity of Cardiovascular Drugs..- A. Introduction.- B. Antihypertensive Drugs.- I. Reserpine.- II. Guanethidine.- C. Vasoconstrictors.- I. Norepinephrine.- II. Angiotensin.- D. Cardiotropic Drugs.- References.- 14 Ganglion-Blocking Agents in Internal Medicine..- A. Introduction.- B. Ganglion-Blocking Agents in the Treatment of Hypertension.- I. Haemodynamic Effects.- II. Dosage of Methonium Compounds.- III. Results of Treatment.- IV. CNS Effects.- V. Effects on the Endocrine System.- VI. Undesirable Side Effects.- VII. Oral Dosage of Methonium Preparations.- VIII. Other Ganglion-Blocking Agents for Oral Use.- IX. Recent Developments.- X. Contraindications.- C. Ganglion-Blocking Agents in the Treatment of Peptic Ulcer.- I. Combination of Ganglion-Blocking Agents With Other Preparations.- References.- 15 Ganglion-Blocking Agents in Anaesthesiology..- A. Introduction.- B. General Characteristics of the Use of Ganglion-Blocking Agents for Artificial Hypotension.- I. Indications for the Use of Ganglion-Blocking Agents.- II. Contraindications for the Use of Ganglion-Blocking Agents.- III. Method of Artificial Hypotension.- 1. Drugs.- 2. Degree and Duration of Artificial Hypotension.- 3. Complications.- C. Use of Artificial Vasodilatation for Various Surgical Interventions and Pulmonary Oedema.- I. Coarctation of the Aorta.- II. Patent Arterial Duct.- III. Heart Disease Correction With Extracorporeal Circulation.- 1. Technique of Artificial Vasodilatation During Cardiopulmonary By-Pass.- IV. Pulmonary Oedema.- 1. Technique of Ganglion Blockade in Pulmonary Oedema.- V. Neurosurgery.- 1. Special Features of the Use of Ganglion-Blocking Agents During Brain Surgery.- References.- Author Index. V.V. Maisky.- Subject Index. V. V. Maisky.