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The Pharmacology of Sleep Разгледай
The Pharmacology of SleepThe Pharmacology of SleepThe Pharmacology of Sleep

The Pharmacology of Sleep

Handbook of Experimental Pharmacology. Volume 116

Anthony Kales

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Ключови думи:  The Pharmacology of Sleep, Anthony Kales, Springer, Handbook of Experimental Pharmacology
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Preface
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 neurotransmitter 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 chronopharmacologic changes.
The second part reviews the role of various neurotransmitter systems in the regulation of sleep and wakefulness. Intact monoaminergic (catecholaminergic, serotonergic, and histaminergic) systems are necessary for the normal expression of both sleep and wakefulness, as well as the different sleep stages. Intact catecholamine transmission is necessary for realization of REM sleep, while noradrenergic neurons playa modulatory role in wakefulness and in the occurrence of REM sleep. Similarly, serotonin acts as a neuromodulator with a very complex role. Specifically, during wakefulness, the activated serotoninergic system participates in creating the conditions for sleep occurrence, while during sleep the deactivated serotoninergic system facilitates in the occurrence of REM sleep. The histaminergic system has an important role in the regulation of the waking state as its pathways resemble those of the ascending noradrenergic and serotonergic components of the reticular activating system. In addition, histamine may act to modulate REM sleep. Finally, it appears that the cholinergic system has a central role in at least two major functions: generation of REM sleep; and activation of the thalamus, cerebral cortex, and hippocampus during both wakefulness
and REM sleep.
The second part continues with a description of the role GABAergic interneurons play in inhibiting most neuronal systems that underlie the sleep-wakefulness cycle. It appears that enhancement of central GABAmediated inhibition by benzodiazepines is the primary mechanism for their hypnotic properties. Several CNS peptides have been shown to possess sleep-modulating activities, although their precise role in sleep regulation requires further investigation of the dynamic interactions among these and other substances. Current evidence indicates that both circadian rhythmicity and sleep inputs can be recognized in the 24-h profiles of all pituitary and pituitary-dependent hormones, while hormones which are not directly controlled by the hypothalamopituitary axis also show consistent changes during sleep and wakefulness. Hormones also may affect sleep and be of functional significance to the maintenance and quality of sleep. Finally, in several animal species, adenosine and adenosine analogs have been shown to produce a hypnotic effect and to affect sleep by increasing both slow-wave and REM sleep.
The third and final part of this volume reviews the clinical pharmacology of sleep. It begins with a review of the methodologic issues relevant for evaluation of hypnotic drugs and stresses the importance of sleep laboratory studies that provide objective and precise measurements throughout the night. Hypnotic efficacy, development of tolerance for hypnotic efficacy, adverse events and withdrawal effects associated with the use of benzodiazepines and related drugs are highly related to their pharmacokinetic and pharmacodynamic properties as well as other special characteristics related to their chemical structures. Various anxiolytic agents, including benzodiazepines, have also been assessed in the sleep laboratory for their efficacy and side effects.
Central stimulants have long been used to maintain wakefulness and alertness. Currently, these drugs are used for the treatment of disorders of excessive sleepiness such as narcolepsy, idiopathic hypersomnia, and other hypersomniac conditions. Most neuroleptics possess sedative effects; however, tolerance to this sedation develops quickly. While, traditionally, antihistamines have been associated with sedative effects, more recently, antihistamine drugs have been developed without this side effect. Most antidepressant drugs suppress REM sleep. If a cholinergic-aminergic neurotransmitter imbalance is assumed to cause depressive and manic states, then the REM sleep abnormalities often observed in depressed patients may be considered as the result of cholinergic hyperfunction or muscarinic supersensitivity. There is considerable information on the clinical pharmacology of anti epileptic drugs, which are a heterogeneous group. However, data on the effects of anti epileptic drugs on human sleep are relatively scarce, partly because of a complex interaction between sleep and epilepsy itself.
In the development of benzodiazepine dependence, dose and duration of administration are well-recognized factors while half-life, binding affinity, and specific chemical structure are less recognized but important factors. Finally, sleep disturbances can be caused by a large variety of therapeutic drugs. Dose and route of administration, as well as the pharmacokinetic and pharmacodynamic properties and chemical structures of various drugs, are major contributing factors to explain differences in the potential of drugs to produce sleep disturbances.
Finally, I am indebted to the authors for their extraordinary efforts in writing outstanding and careful reviews of the literature, thereby making this volume an important contribution to the field of the pharmacology of sleep and wakefulness.

Evolution of Concepts of Mechanisms of Sleep
Principles of Sleep Regulation: Implications for the Effect
of Hypnotics on Sleep
Principles of Chronopharmacology and the Sleep-Wake Rhythm
Pharmacology of the Catecholaminergic System
The Serotoninergic System and Sleep-Wakefulness Regulation
Pharmacology of the Histaminergic System
Pharmacology of the Cholinergic System
Pharmacology of the GABAergic/Benzodiazepine System
Pharmacology of the eNS Peptides
Hormones and Sleep
Pharmacology of the Adenosine System
Methodological Issues in Pharmacological Studies of Sleep
Hypnotic Drugs
Anxiolytic Drugs
Stimulant Drugs
Neuroleptics, Antihistamines and Antiparkinsonian Drugs:
Effects on Sleep
Antidepressant and Antimanic Drugs
Anticonvulsant Drugs
Mechanisms of Benzodiazepine Drug Dependence
Sleep Disturbances as Side Effects of Therapeutic Drugs

With 56 fugures and 26 tables.
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