Inhalt

1 Antihypertensive Drugs.- I. Introduction.- II. Requirements for an Antihypertensive Agent.- III. Combinations of Antihypertensive Drugs.- IV. Trends in Antihypertensive Therapy.- V. National Preferences of Treatment Schemes.- VI. Experimental Hypertension.- References.- 2 The Chemistry of Antihypertensive Agents.- I. Early Antihypertensives.- II. Adrenergic Neuronal Blockers: Guanethidine and Similar Compounds.- A. SU 4029 and Guanethidine.- B. Modification of the Guanethidine Structure.- III. Rauwolfia Alkaloids.- IV. Ganglionic Blockers.- V. Clonidine, ST 155, 2-(2, 6-dichlorophenylamino)-2-imidazoline and Analogs.- VI. The Chemistry of the Veratrum Alkaloids.- VII. Compounds Acting Directly on Vascular Smooth Muscles.- VIII. The ?-Adrenolytics (?-Adrenergic Receptor Blocking Agents).- IX. Fusaric Acid.- References.- 3 Ganglion-Blocking Drugs in Antihypertensive Therapy.- I. Introduction.- II. Characteristics of Individual Drugs, Generic, and Brand Names, Routes of Administration, and Dosages.- A. General Remarks.- B. Quaternary Ganglionic Blockers.- C. Nonquaternary Ganglionic Blockers.- III. Pharmacokinetics.- A. Methonium Compounds.- B. Mecamylamine and Pempidine.- C. Other Drugs.- IV. Mode of Action.- A. Principles of Ganglionic Transmission.- B. Drug-Induced Ganglionic Blockade.- C. Nonselective Interference with Sympathetic and Parasympathetic Transmission.- D. Effects on the Cardiovascular System.- E. Tolerance to Antihypertensive Activity.- F. Pharmacologic Effects Unrelated to Ganglionic Blockade.- V. Side-Effects.- A. General Remarks.- B. Side-Effects Due to Blockade of the Autonomic Nervous System.- C. Side-Effects Unrelated to Ganglionic Blockade.- VI. Present Role of Ganglion-Blocking Drugs.- References.- 4 The Pharmacology of Rauwolfia Alkaloids.- I. Introduction and History.- II. Absorption, Metabolism, and Distribution of Reserpine.- III. Effects of Reserpine on Levels of Catecholamines and Serotonin in Tissues.- A. Sympathetically Innervated Tissues.- B. Tissue Chromaffin Cells.- C. Adrenal Medullary Amines.- D. Peripheral Serotonin.- E. Central Nervous System.- IV. Effects of Reserpine on Uptake, Storage, Synthesis and Catabolism of Catecholamines and Serotonin.- A. Effect of Reserpine on Uptake of Amines.- B. Effect of Reserpine on Amine Storage Mechanisms.- C. Effect of Reserpine on Retention of Amines by Isolated Storage Particles.- D. Effect of Reserpine on the Synthesis of Catecholamines and Serotonin.- E. Effect of Reserpine on Catabolism of Catecholamines and Serotonin.- F. Recovery of Amine Stores After Reserpine Treatment.- V. Effect of Reserpine on Other Neurotransmitters and Auracoids.- A. Acetylcholine.- B. Histamine.- C. Tryptamine.- VI. Effects of Reserpine on Function of Peripheral Tissues.- A. Effect of Reserpine on Adrenergic Mechanisms.- B. Effects of Reserpine on Cardiac and Smooth Muscle Function.- C. Reserpine-Induced Supersensitivity.- VII. Effects of Reserpine on Central Nervous Function.- A. The Sedative and Tranquillizing Activity of Reserpine.- B. Extrapyramidal Effects of Reserpine.- C. Effect of Reserpine on Body Temperature.- D. Electrical Activity of the Brain.- E. Effects of Reserpine on Reflexes and Centrally Maintained Autonomic Nervous Tone.- F. Recovery from the Central Actions of Reserpine.- G. Interaction Between Reserpine and Other Centrally Acting Drugs.- VIII. Endocrinological, Metabolic and Structural Effects of Reserpine.- A. Effects of Reserpine on Endocrine Systems.- B. Electrolyte Metabolism.- C. Tissue Metabolism.- D. Structural Effects.- References.- 5 Adrenergic Neuron Blocking Drugs.- I. Introduction to Adrenergic Neuron Blocking Agents.- A. General Pharmacology.- B. History of Development.- C. Therapeutic Use in Hypertension.- II. Distribution of Neurin Blocking Agents in Tissues Following Their Administration to Animals and Man.- III. Interactions of Neuron Blocking Agents with Adrenergic Neurons.- A. Retention by Adrenergic Neurons.- B. Mechanism of Uptake into Adrenergic Neurons.- C. Storage in Adrenergic Neurons.- D. Release from Adrenergic Neurons.- IV. Interactions of Neuron Blocking Agents with Norepinephrine in Adrenergic Neurons.- A. Capacity to Release Norepinephrine from Nerve Endings and Simultaneously to Inhibit the Release of Norepinephrine Elicited by Sympathetic Neuronal Activity.- B. Effect on the Norepinephrine Content of Adrenergically Innervated Organs and the Adrenal Medulla.- C. Effects on Synthesis and Degradation of Norepinephrine in Adrenergic Neurons.- D. Effect on the Uptake of Norepinephrine into Adrenergic Nerves, Storage of Norepinephrine in and Release from Intraneuronal Granules, and Disappearance of Norepinephrine from Adrenergic Nerves.- V. Hypotheses Regarding the Mechanism of Neuron Blockade.- A. Subcellular Pool Depletion Hypothesis.- B. Membrane Depolarizing and Stabilizing Hypotheses and Local Anesthetic Action.- C. Cholinergic Link Hypothesis and the Possible Role of Ca-Ion.- D. Amphetamine Receptor Site Hypothesis.- E. MAO Inhibition Hypothesis.- F. False Transmitter Hypothesis.- VI. Absorption, Metabolism and Excretion of Neuron Blocking Agents.- A. Guanethidine.- B. Bretylium.- C. Bethanidine.- D. Debrisoquin.- E. Guanoxan.- VII. Actions of Adrenergic Neuron Blocking Agents in Tissues and Organs.- A. General Sympathomimetic Action.- B. General Potentiation of the Responses to Norepinephrine and Closely Related Pressor Amines and Inhibition of Tyramine and Other Indirectly-Acting Phenethylamines.- C. Vascular Smooth Muscle.- D. Cardiac Muscle.- E. Neuromuscular Junction.- F. Influence on Frequency-Response Curves for Several Nerve-Smooth Muscle Preparations.- G. Actions on Excitable Membranes of Nerve Trunks.- H. Effects at Synapses.- I. Central Nervous System.- J. Additional Biochemical Effects.- K. Structural and Ultrastructural Changes in Neurons.- L. Effects on the Interaction Between Sympathetic and Parasympathetic Nervous Systems.- M. Effects on Degeneration Phenomena Following Section of Post Ganglionic Sympathetic Nerves.- N. Effects on Plasma Volume and Kidney Function.- O. Mast Cells and Platelets.- P. Effects on Extraneuronal Uptake of Norepinephrine.- VIII. The Amine Pump in Peripheral Adrenergic Nerves.- A. Some Problems Discussed.- B. The "Amine Pump Receptor".- IX. Authors' Perspective.- References.- 6 False Transmitters as Antihypertensive Agents.- I. Catecholamine Metabolism.- A. Ring Hydroxylation.- B. Decarboxylation: Dopa Decarboxylase.- C. Aliphatic Side-Chain Hydroxylation: Dopamine-?-Hydroxylase.- D. N-Methylation: Phenethanolamine-N-Methyl Transferase.- E. Amine Oxidation: Monoamine Oxidase.- F. m-O-Methylation: Catechol-O-Methyltransferase.- II. Catecholamine Storage and Release.- III. Uptake of Amines Through the Cell Membrane.- IV. False Transmitters and Sympathetic Transmission.- V. False Transmitters and Blood Pressure.- A. Methyldopa.- B. Dopa and m-Tyrosine.- C. ?-Methyl-m-Tyrosine.- References.- 7 The Pharmacology of Clonidine and Related Products.- I. Introduction.- II. Chemistry.- III. Principal Pharmacological Properties.- IV. Effects on the Sympathetic System.- A. ?-Sympathomimetic Effect.- B. Effects on Catecholamines.- C. Influence on Noradrenaline Levels and Metabolism at Peripheral Sites.- D. Effects on Postganglionic Sympathetic Fibers.- E. Centrally Mediated Decrease in Sympathetic Tone as the Cause of Hypotension.- F. Sites of Action in the Central Nervous System.- G. Effects of Clonidine on Centrally Mediated Increases in Sympathetic Tone.- H. Effects of Clonidine on Centrally Mediated Depressor Responses.- J. Effects of Clonidine on Cardiovascular Reflexes.- K. Evidence for Activation of a Central ?-Sympathomimetic Mechanism as the Cause of the Sympatho-Inhibitory Effect of Clonidine.- L. Discrepancies Between the Decrease in Blood Pressure and the Reduction in Sympathetic Nerve Activity.- M. Interferences Between Clonidine, Neuroleptic and Antidepressant Agents.- V. Effects on…