D.A. KHARKEVICH The history of the study of ganglionic substances begins with the paper of LANGLEY and DICKINSON (1889), who established the ability of nicotine to block the neurones in the superior cervical ganglion. This was a considerable discovery as the authors ascertained that impulses were transmitted from pre- to postganglionic neurones in the autonomic ganglia. Simultaneously they indicated the possibility of pharmaco­ logical influence upon interneuronal transmission in autonomic ganglia. The idea of ganglionic receptors specifically sensitive to nicotine followed logically. Later, LANGLEY (1905, 1906) considered the problem of receptors with respect to neuro-effector synapses. It is remarkable that he was one of the first to put forward the theory of chemical mediation of excitation (" ... the nervous impulse should not pass from nerve to muscle by an electric discharge, but by the secretion of a special substance at the end of the nerve": LANGLEY, 1906, p. 183). In addition, LANGLEY JOHN N. LANGLEY (1852-1926) D.A. KHARKEVICH 2 and his collaborators managed to define the topography of autonomic ganglia more precisely by means of nicotine. It should be mentioned that it was he who introduced the terms "autonomic nervous system" and "parasympathetic nervous system".

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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.- …