The Pharmacology of Sleep

ISBN-13: 9783540589617 / Angielski / Twarda / 1995 / 583 str.

Anthony Kales; Anthony Kales; J. Adrien

Opis

The last four decades have witnessed considerable advances in our knowledge of the pharmacology of sleep. Both basic and clinical pharmacology have made major contributions toward our current understanding of the complex mechanisms of sleep and wakefulness. In addition, these advances in our understanding of the pharmacology of sleep have benefited the treatment of sleep disorders and various neurologic and psychiatric conditions. This volume is organized into three different parts. The first is a review of the basic mechanisms of sleep and wakefulness and the chronobiology of sleep. The second part reviews the basic pharmacology of the various neuro- transmitter systems involved in sleep and wakefulness, while the third is clinically oriented and focuses on the effects of a variety of drugs on sleep and wakefulness. The initial part begins with a historical review of the hypotheses of the mechanisms of sleep, evolving from passive to active regulation, and concepts involving sleep-related neurotransmitters and other sleep factors. Then regulation of sleep and wakefulness is discussed in terms of homeostatic, circadian, and ultradian processes. Also discussed is the fact that sleep homeostasis is not disrupted by the administration of hypnotic drugs. This part also reviews time-dependent properties of pharmacologic agents in relation to endogenous biologic rhythms and more specifically to chrono- pharmacologic changes.

Spis treści

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 Circadian Programmer?.- I. Research Background.- II. Distribution and Biosynthesis in the Brain.- III. Circadian Sleep-Waking Rhythm.- IV. Sleep-Promoting Activity of Structural Analogs.- V. Aspects of “Extra-Sleep”Activities and Neurotransmitter Systems.- 1. Antinociceptive Activity and Sleep.- 2. Thermoregulation.- VI. Concluding Remarks.- C. Glutathione: A Neuronal Detoxification Factor?.- I. Research Background.- II. Sleep-Modulatory Activity of Oxidized Glutathione.- 1. Bioassay.- 2. Effects on Sleep.- 3. Effects on Brain Temperature.- III. Sleep-Modulatory Activity of Reduced Glutathione.- IV. Possible Mechanisms.- D. Muramyl Peptides and Cytokines: Somnopyrogenic Immunomodulators?.- I. Research Background.- II. Muramyl Peptides and Infectious Diseases.- 1. Bacterial and Viral Infections and Sleep.- 2. Cerebral Site of Action.- III. Interleukin-1.- 1. Somnopyrogenic Activities.- 2. Transport.- 3. IL-1 Receptors.- 4. Interactions with Other Sleep Substances.- IV. Tumor Necrosis Factor.- V. Interferon.- VI. Integrative Remarks.- E. Hypothalamo-hypophyseal Hormones: Neuroendocrine Transducers?.- I. Research Background.- II. Growth Hormone-Related Hormones.- III. Corticotropin-Related Hormones.- IV. Thyrotropin-Related Hormones.- V. Prolactin.- VI. Concluding Remarks.- F. Satiety-Related Substances: Ischymetric Factors or Postprandial Somnogens?.- I. Research Background.- II. Cholecystokinin.- III. Bombesin.- IV. Acidic Fibroblast Growth Factor.- V. Concluding Remarks.- G. Vasoactive Intestinal Polypeptide and Vasopressin: Circadian Timekeepers or REM Sleep Factors?.- H. Vasotocin: A Brain Maturation Modulator?.- I. General Concluding Remarks.- J. Summary.- References.- 10 Hormones and Sleep.- A. Introduction.- B. Interactions Between Sleep, Circadian Rhythmicity and Hormonal Release.- C. Methodology of Studies of Sleep and Hormonal Secretion.- I. Design of Experimental Protocols.- II. Analysis of Hormonal Data.- III. Analysis of the Interaction Between Sleep and Hormonal Release.- D. Modulation of Hormonal Release by Sleep and Wake.- I. Corticotropic Axis.- II. Somatotropic Axis.- III. Thyrotropic Axis.- IV. Lactotropic Axis.- V. Gonadotropic Axis.- VI. Glucose Tolerance and Insulin Secretion.- VII. Hormones Regulating Water Balance.- E. Sleep-Promoting Effects of Hormones.- I. Growth Hormone-Releasing Hormone and Growth Hormone.- II. Melatonin.- F. Conclusions.- G. Summary.- References.- 11 Pharmacology of the Adenosine System.- A. Introduction.- B. Effects of Adenosine and Adenosine-Related Compounds on Sleep.- I. Intracerebroventricular Administration of Adenosine and Sleep in Rats.- II. Microinjections of Adenosine to Preoptic Area and Sleep in Rats.- III. Inhibition of Adenosine Deaminase and Sleep.- IV. Adenosine Analogs and Sleep.- C. Adenosine A1 Receptors in Sleep and Waking.- I. Central A1 Receptor Variation During the Circadian Period.- II. Central A1 Receptors in Young and Old Rats.- III. Central A1 Receptors in REM Sleep Deprivation.- D. Methylxanthines and Sleep: Effects of Blockade of Adenosine A1 and/or Adenosine A2 Receptors.- I. Caffeine and Adenosine Agonists: Behavioral Interaction.- II. Dose-Response Effects of Caffeine on Sleep.- III. Caffeine Blocks Both Adenosine A1 and A2 Receptors: Is the Blockade of A1 Receptors More Important for CNS Stimulation?.- E. Benzodiazepines and Central Adenosine Receptors.- I. Diazepam and Adenosine Receptors in Specific Brain Areas in Rats.- II. Triazolam and Central Adenosine Receptors.- III. Inhibition of Adenosine Transport and Central Adenosine Receptors.- F. Hypothesis for Adenosine Hypnotic Action.- G. Conclusions.- H. Summary.- References.- 12 Methodological Issues in Pharmacological Studies of Sleep.- A. Introduction.- B. Objectives of the Phases of Investigation of a New Hypnotic.- C. Methods of Measurement.- I. Pharmacokinetic.- II. Efficacy.- 1. Objective Measures.- 2. Subjective Estimates.- III. Safety.- 1. Objective Measures.- 2. Patient Reports.- D. Design and Analysis Considerations.- I. Phase I Studies.- II. Phase II Studies.- 1. Design of Phase II Studies.- 2. General Issues: Sleep Laboratory Studies.- 3. General Issues: Clinical Trials.- 4. General Issues: Studies of Effects on Daytime Performance.- III. Phase III Studies.- IV. Phase IV Studies.- E. Summary.- References.- 13 Hypnotic Drugs.- A. Introduction.- B. The Condition of Insomnia.- I. Treatment of Insomnia.- C. Development of Benzodiazepines and Other Hypnotic Drugs.- I. Evaluation of Hypnotic Drugs.- D. 1,4-Benzodiazepines with Slow Elimination and Low Binding Affinity.- I. Flurazepam.- 1. Efficacy.- 2. Withdrawal Effects.- 3. Side Effects.- II. Quazepam.- 1. Efficacy.- 2. Withdrawal Effects.- 3. Side Effects.- E. 1,4-Benzodiazepines with Intermediate to Slow Elimination and Moderate Binding Affinity.- I. Nitrazepam.- 1. Efficacy.- 2. Withdrawal Effects.- 3. Side Effects.- F. 1,4-Benzodiazepines with Rapid to Intermediate Elimination and Low Binding Affinity.- I. Temazepam.- 1. Efficacy.- 2. Withdrawal Effects.- 3. Side Effects.- G. 1,4-Benzodiazepines with Rapid to Intermediate Elimination and Moderate to High Binding Affinity.- I. Flunitrazepam.- 1. Efficacy.- 2. Withdrawal Effects.- 3. Side Effects.- II. Loprazolam.- 1. Efficacy.- 2. Withdrawal Effects.- 3. Side Effects.- III. Lormetazepam.- 1. Efficacy.- 2. Withdrawal Effects.- 3. Side Effects.- H. 1,4-Benzodiazepines with Rapid Elimination and High Binding Affinity.- I. Midazolam.- 1. Efficacy.- 2. Withdrawal Effects.- 3. Side Effects.- I. Triazolobenzodiazepines.- I. Brotizolam.- 1. Efficacy.- 2. Withdrawal Effects.- 3. Side Effects.- II. Estazolam.- 1. Efficacy.- 2. Withdrawal Effects.- 3. Side Effects.- III. Triazolam.- 1. Efficacy.- 2. Withdrawal Effects.- 3. Side Effects.- J. New Non-Benzodiazepine Hypnotics.- I. Zopiclone.- 1. Efficacy.- 2. Withdrawal Effects.- 3. Side Effects.- II. Zolpidem.- 1. Efficacy.- 2. Withdrawal Effects.- 3. Side Effects.- K. Conclusions on Efficacy of Hypnotic Drugs.- L. Conclusions on Underlying Mechanisms for Adverse Events.- I. Pharmacokinetic Factors.- II. Pharmacodynamic Factors.- III. Special Properties Related to Chemical Structure.- M. Comments on Drug-Induced Sleep Stage Alterations.- N. Summary.- References.- 14 Anxiolytic Drugs.- A. Introduction.- B. Anxiolytic Drugs and Sleep: Overview.- C. Benzodiazepines.- I. 1,4-Benzodiazepines with Slow Elimination and Low Binding Affinity.- 1. Ketazolam.- 2. Chlordiazepoxide.- 3. Clorazepate.- 4. Fosazepam.- II. 1,4-Benzodiazepines with Intermediate to Slow Elimination and Moderate to High Binding Affinity.- 1. Clonazepam.- 2. Diazepam.- III. 1,4-Benzodiazepines with Rapid to Intermediate Elimination and Low Binding Affinity.- 1. Oxazepam.- IV. 1,4-Benzodiazepines with Rapid to Intermediate Elimination and Moderate to High Binding Affinity.- 1. Lorazepam.- V. Triazolobenzodiazepines.- 1. Alprazolam.- 2. Adinazolam.- D. Non-Benzodiazepines, GABAA Agonists.- I. Cyclopyrrolons.- 1. Suriclone.- II. Imidazopyridines.- 1. Alpidem.- E. ?-Adrenoceptor Antagonists.- I. ?-Blockers with High Lipophilicity.- 1. Propranolol.- II. ?-Blockers with Moderate Lipophilicity.- 1. Metoprolol.- 2. Pindolol.- III. ?-Blockers with Low Lipophilicity.- 1. Acebutolol.- 2. Atenolol.- 3. Nadolol.- 4. Sotalol.- F. ?2-Receptor-Agonists.- I. Clonidine.- 1. Efficacy.- 2. Withdrawal Effects.- 3. Side Effects.- II. Guanfacine.- 1. Efficacy.- 2. Withdrawal Effects.- 3. Side Effects.- G. Serotonin Receptor-Agonists.- I. Buspirone.- 1. Efficacy.- 2. Withdrawal Effects.- 3. Side Effects.- H. Serotonin Receptor-Antagonists.- I. Ritanserin.- 1. Efficacy.- 2. Withdrawal Effects.- 3. Side Effects.- I. Summary.- References.- 15 Stimulant Drugs.- A. Early Use of Plant Preparations Containing Central Stimulants.- B. Indications for Medical Use of Central Stimulant Drugs.- C. Clinical Features of Narcolepsy and Other Hypersomniac Conditions.- I. Narcolepsy.- II. Idiopathic Hypersomnia.- III. Recurrent Hypersomnia.- D. Central Stimulants.- I. Caffeine.- II. Ephedrine.- III. Amphetamine and Methamphetamine.- IV. Methylphenidate.- V. Pemoline.- VI. Mazindol.- VII. Modafinil.- E. Treatment of Narcolepsy and Other Hypersomniac Conditions with Central Stimulants and Other Adjunctive Drugs.- I. Narcolepsy.- II. Idiopathic Hypersomnia.- III. Recurrent Hypersomnia.- F. Other Problems Related to the Use of Central Stimulant Drugs.- G. Summary.- References.- 16 Neuroleptics, Antihistamines and Antiparkinsonian Drugs: Effects on Sleep.- A. Introduction.- B. Neuroleptics.- I. Introduction.- II. Phenothiazines.- 1. Chlorpromazine.- 2. Other Phenothiazines.- III. Butyrophenones.- IV. Nonclassical Neuroleptics.- 1. Sulpiride.- 2. Clozapine.- 3. Remoxipride.- 4. Ritanserin.- V. Clinical Implications.- C. Antihistamines.- I. Introduction.- II. Sedative Antihistamines.- III. Nonsedative Antihistamines.- IV. Clinical Implications.- D. Antiparkinsonian Drugs.- I. Introduction.- II. Dopaminergic Antiparkinsonian Drugs.- III. Anticholinergic Antiparkinsonian Drugs.- IV. Clinical Implications.- E. Summary.- References.- 17 Antidepressant and Antimanic Drugs.- A. Introduction.- B. The Antidepressant Drugs.- I. Mechanisms of Action.- II. Classification.- 1. Sedative and Nonsedative Antidepressants.- 2. Effects on Norepinephrine, Dopamine and Serotonin.- III. An Integrative Model for Depression.- IV. Sleep and Depression.- V. Effects of Antidepressants on Sleep.- 1. Effects of Antidepressants on REM Sleep.- 2. Effects of Antidepressants on Other Sleep Stages.- VI. Use of Antidepressants in Sleep-Related Disorders.- 1. Psychophysiological Insomnia.- 2. Sleep Apnea Syndrome.- 3. Narcolepsy.- C. Antimanic Drugs.- I. Lithium.- II. Carbamazepine.- D. Summary.- References.- 18 Anticonvulsant Drugs.- A. Introduction.- B. Drug Reviews.- I. Phenobarbital.- II. Phenytoin.- III. Carbamazepine.- IV. Valproate.- V. Ethosuximide.- C. Summary.- References.- 19 Mechanisms of Benzodiazepine Drug Dependence.- A. Introduction.- B. Prevalence of Benzodiazepine Dependence.- C. Description of Benzodiazepine-Withdrawal Symptoms.- I. Most Frequent Withdrawal Symptoms Associated with Benzodiazepine Use and Discontinuation.- 1. Daytime Anxiety, Early Morning Insomnia and Other Hyperexcitability Phenomena During Drug Administration.- 2. Rebound Insomnia and Anxiety Following Drug Withdrawal.- II. Less Frequent but Severe Withdrawal Phenomena Following Benzodiazepine Discontinuation.- D. Risk Factors Associated with Benzodiazepine Dependence.- I. Dose.- II. Duration of Drug Administration.- III. Gradual Versus Abrupt Discontinuation.- IV. Benzodiazepine Dependence and Patient Type.- 1. Subjects with Substance Abuse Disorders.- 2. Subjects with Psychiatric Disorders.- 3. Subjects with Sleep Disorders.- E. Pharmacological Properties Associated with Benzodiazepine Dependence.- I. Absorption Rate.- II. Elimination Rate.- III. Receptor-Binding Affinity.- IV. Benzodiazepine Effects on the LC-NE and HP A Axes.- 1. Tolerance, Daytime Anxiety and Other Hyperexcitability Phenomena During Drug Administration.- 2. Withdrawal Difficulties (Rebound Insomnia and Anxiety and Seizures).- V. Role of Other Neurotransmitters in Benzodiazepine Dependence.- VI. Conclusions.- F. Summary.- References.- 20 Sleep Disturbances as Side Effects of Therapeutic Drugs.- A. Factors Contributing to a Drug’s Capacity to Induce Sleep Disturbances.- B. Insomnia.- I. Stimulants.- II. Stimulant Antidepressants.- III. Hypnotics and Anxiolytics.- 1. Drug Withdrawal Insomnia.- 2. Early Morning Insomnia and Daytime Anxiety.- 3. Rebound Insomnia and Rebound Anxiety.- 4. Sleep Disturbances with Newer Anxiolytics.- IV. Corticosteroids.- V. Bronchodilators.- VI. Antihypertensives.- VII. Other Drugs.- C. Excessive Daytime Sleepiness.- I. Hypnotics and Anxiolytics.- II. Sedative Neuroleptics.- III. Sedative Antidepressants.- IV. Anticonvulsants.- V. Antihistamines.- D. Sleep Apnea.- I. CNS Depressants.- 1. Hypnotics.- 2. Narcotics.- 3. Anesthetics.- II. Antihypertensives.- III. Testosterone.- IV. Other Drugs.- E. Nocturnal Myoclonus.- F. Auxiliary Symptoms of Narcolepsy.- G. Somnambulism/Night Terrors.- I. Lithium.- II. Hypnotics.- III. Other Drugs.- H. REM Behavior Disorder.- I. Nightmares.- I. Antihypertensives.- II. Psychotropic Drugs.- III. Other Drugs.- J. Circadian Rhythm Disorders.- K. Summary.- References.