The Pharmacology of Sleep

A review of the current state of the clinical and basic science of the pharmacology of sleep. The information provided ranges from a historical perspective to current concepts of sleep mechanisms, including the interaction between pharmacology and sleep-wake regulation and between chronopahrmacology and sleep-wake rhythms. For the first time in one single volume, both the basic mechanisms of sleep, and the basic and clinical aspects of the pharmacology of sleep are dealt with in a thorough, comprehensive and authoritative manner. The chapters, written by the foremost scientific authorities in this field, integrate the latest information on the basic mechanisms of drugs as they relate to their effects on sleep.

Inhalt

1 Evolution of Concepts of Mechanisms of Sleep.- A. Introduction.- B. Brief Historical Overview.- C. Early Neurophysiological Concepts of Sleep (From Passive to Active).- D. Neurohumoral Concepts of Sleep Regulation.- I. Progressive Development of an Old Idea.- II. Sleep Factor Regulation Viewed Physiologically.- E. Neurochemical - Neurophysiological Concepts of Sleep Regulation.- I. Classical Neurotransmitters.- II. Neurotransmitters and Single-Unit Studies.- F. Final Considerations.- G. Summary.- References.- 2 Principles of Sleep Regulation: Implications for the Effect of Hypnotics on Sleep.- A. Basic Processes.- B. Sleep Homeostasis.- I. EEG Slow Waves as Indicators of "Sleep Pressure".- 1. Global Changes During Baseline Sleep Episodes.- 2. Effect of Sleep Deprivation.- II. Ultradian Dynamics of Slow-Wave Activity and Spindle Activity.- 1. Baseline Sleep and Recovery Sleep After Sleep Deprivation.- 2. Neurophysiological Basis of Slow Waves and Sleep Spindles.- III. Homeostasis of REM Sleep and Interactions with Non-REM Sleep.- C. Effect of Hypnotics on Sleep and the Sleep EEG.- I. Benzodiazepine Hypnotics Alter the Sleep EEG.- II. Benzodiazepine-Receptor Agonists Have Similar Effects on the Sleep EEG.- III. Do Hypnotics Disrupt Sleep Homeostasis?.- IV. Effect of Benzodiazepine Hypnotics on Circadian Rhythms.- D. Concluding Remarks: Pitfalls in Pharmacological Sleep Studies.- E. Summary.- References.- 3 Principles of Chronopharmacology and the Sleep-Wake Rhythm.- A. Introduction.- B. Properties of Biological Rhythms.- C. Biological Rhythms as Adaptive Phenomena to Predictable Changes in Environmental Factors.- D. Temporal Distribution and Dosing Time of Therapies.- E. Concepts in Chronopharmacology.- I. Chronopharmacokinetics (or Chronokinetics) of a Drug.- II. Biomechanisms Presumably Involved in Chronokinetic Changes.- III. Chronesthesy of a Biosystem.- IV. Chronergy of a Chemical Agent.- V. Chronotherapy.- F. Drug Effects on Sleep, Anesthesia and Related Processes.- I. Anesthetics.- II. Ethanol.- III. Drug-Induced Drowsiness.- G. Shift Workers, Jet Lag and Sleeping Pills.- I. Shift Workers and Sleeping Pills.- II. Jet Lag, Sleeping Pills, Melatonin and Bright Light.- H. Summary.- References.- 4 Pharmacology of the Catecholaminergic System.- A. Introduction.- B. Amine-Depleting and Synthesis-Inhibiting Substances.- I. Catecholaminergic-Depleting Substances: Reserpine.- II. Dopamine-ß-hydroxylase Inhibitors.- III. Tyrosine Hydroxylase Inhibitor.- IV. Norepinephrine Uptake Blockers.- V. In Conclusion.- C. Adrenergic Agonists and Antagonists.- I. ?1-Antagonists (Phenoxybenzamine, Prazosin).- II. ?1-Agonist.- III. ?2-Antagonists (Phentolamine, Yohimbine).- IV. ?2-Agonist.- V. ?-Adrenergic Antagonists.- VI. ?-Adrenergic Agonists.- VII. In Conclusion.- D. Dopamine Agonists and Antagonists.- I. Dopamine2-Agonists.- II. Dopamine2-Antagonists.- III. Dopamine1-Antagonists.- IV. In Conclusion.- E. Differential Regulation of Waking and PS by Catecholamines.- F. Summary.- References.- 5 The Serotoninergic System and Sleep-Wakefulness Regulation.- A. The Serotoninergic System.- I. Serotoninergic Nuclei and Pathways.- II. Serotoninergic Metabolism and Neurotransmission.- 1. Synthesis of Serotonin.- 2. Release and Inactivation of Serotonin.- 3. Impairment of the Synthesis, Release and Catabolism of Serotonin.- III. Serotoninergic Receptors.- 1. 5-HT1A Receptors.- 2. 5-HT2 Receptors.- 3. 5-HT3 Receptors.- 4. 5-HT4 Receptors.- IV. Conclusion.- B. Serotonin and Sleep.- I. Spontaneous Activity of the Serotoninergic System During Sleep and Wakefulness.- II. Pharmacological Impairment of Serotoninergic Neurotransmission.- 1. Enhancement of Serotonin Levels in the Brain.- 2. Decrease in Serotonin Levels in the Brain.- III. Pharmacological Impairment of Receptor Function.- 1. 5-HT1A Receptors.- 2. 5-HT1B and 5-HTlC Receptors.- 3. 5-HT2 Receptors.- 4. 5-HT3 Receptors.- 5. Interaction Between the Various Serotoninergic Receptor Types.- IV. How Is Serotonin Involved in Sleep-Wakefulness Regulation?.- C. Summary.- References.- 6 Pharmacology of the Histaminergic System.- A. Introduction.- B. Histamine Synthesis and Metabolism.- C. Histaminergic Nuclei and Pathways.- D. Histamine Receptors.- E. Effects of Histamine at the Cellular Level.- F. Drugs Acting at the Histamine Receptors.- I. H1 Receptor.- II. H2 Receptor.- III. H3 Receptor.- G. Histamine Control of the Waking State.- I. Electrophysiological Studies.- II. Circadian Rhythms.- III. Lesion Studies.- IV. Pharmacological Studies.- 1. Intracerebroventricular Administration of Histamine.- 2. Histamine Synthesis Inhibition.- 3. H1 Receptor Agonists and Antagonists.- 4. H2 Receptor Agonists and Antagonists.- 5. H3 Receptor Agonists and Antagonists.- H. Summary.- References.- 7 Pharmacology of the Cholinergic System.- A. Introduction.- B. Biochemistry, Anatomy, and Physiology of the Cholinergic System.- I. Biochemistry.- 1. Synthesis.- 2. Storage and Release.- II. Anatomy.- 1. Cholinergic Cells.- 2. Basal Forebrain Cholinergic Groups.- 3. Brain Stem Cholinergic Groups.- III. Cholinergic Receptors.- 1. Nicotinic Receptors.- 2. Muscarinic Receptors.- IV. Postsynaptic Effects.- C. Cholinergic System and Sleep.- I. Spontaneous Activity of Cholinergic Neurons.- 1. Nucleus Basalis.- 2. LDT/PPT.- II. Spontaneous Release of Ach.- III. Availability of Cholinergic Receptors and AChE.- IV. Lesions of the Cholinergic System.- 1. Lesions and Stimulation of Basal Forebrain.- 2. Lesions of LDT/PPT.- V. Pharmacological Manipulations of the Cholinergic System.- 1. Cortical Activation.- 2. Hippocampal Theta Rhythm.- 3. REM Sleep.- 4. ACh and Atonia.- 5. ACh and PGO Waves.- 6. Diseases Involving ACh and Sleep.- D. Cholinergic System and Postural Mechanisms.- I. Effects on Decerebrate Rigidity.- II. Effects on Vestibulospinal Reflexes.- III. Effects on Postural Adjustments During Cortically Induced Movements.- IV. Cerebellar Regulation of Vestibular Reflexes.- E. Cholinergic System and Respiratory Mechanisms.- F. Conclusions.- I. Cholinergic System and Cortical Activation.- II. Cholinergic System and REM Sleep.- III. Cholinergic System and Postural Mechanisms.- G. Summary.- References.- 8 Pharmacology of the GABAergic/Benzodiazepine System.- A. Introduction.- B. Functional Evidence for the GABA-mimetic Properties of Benzodiazepines.- I. Electrophysiology.- II. Pharmacology and Biochemistry.- III. Histochemistry.- IV. Receptor Interactions: Effects of GABA Receptor-Agonists on Benzodiazepine-Receptor Binding and Vice Versa.- C. GABAA Receptor - Benzodiazepine Receptor - Chloride Channel Complex.- I. Functional Aspects.- II. Structural Aspects.- III. Chain of Events from Benzodiazepine-Receptor Occupation to Pharmacological Response.- IV. Benzodiazepine-Receptor Ligands with Different Intrinsic Activities: Concept of Agonists, Antagonists, and Inverse Agonists.- V. Receptor Subclassess and Hypnotic Benzodiazepines.- VI. Relationship Between Benzodiazepine-Receptor Affinity and Biological Activity.- D. Specific Hypnotic Drugs.- I. Benzodiazepines.- II. Barbiturates.- III. Zopiclone and Zolpidem.- E. Summary.- References.- 9 Pharmacology of the CNS Peptides.- A. Introduction.- B. Delta-Sleep-Inducing Peptide: A Circadi…