Between 1950 and 1960, remarkable advances were made in the develQpment Qf antihypertensive drugs, but since then, prQgress has been less rapid. This dQes nQt mean that no. new drugs have been intrQduced: Qn the cQntrary, their number has increased sharply; but since the advent Qf the beta-adrenergic blQckers no. new pharmacQdynamic principle has been discQvered that CQuid be applied widely as an antihypertensive. This has nQt been fQr want Qf effQrts, because many attempts have been made to. find new ways and means Qf influencing blQQd pressure regulatiQn Qr the mechanisms invQlved in the pathQgenesis Qf hypertensiQn. HQwever, the results Qf these endeavQrs have mQstly been disapPQinting. Even thQugh high blQQd pressure can be treated mQre satisfactQrily tQday than many Qther diseases, the success achieved in cQmbating Qne Qf man's mQst frequent ailments shQuld nQt induce cQmplacency, but rather stimulate research tQwards further imprQvements. The present standstill affQrds an QPPQrtunity to. review the field Qf antihy pertensive agents, fQr it is unlikely that fundamentally new drugs will appear in the near future. AlthQugh greater knQwledge has been gained Qf the mechanisms Qf blQQd-pressure regulatiQn and Qf the pathQgenesis Qf hypertensiQn, these ad vances have had no. direct cQnsequences in the search fQr new therapeutics.

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 Oxidat…