Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917801 (insomnia)
 10,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As many as 10% of humans suffer chronic sleep disturbances, yet the genetic mechanisms that regulate sleep remain essentially unknown. It is therefore crucial to develop simple and cost-effective vertebrate models to study the genetic regulation of sleep. The best characterized mammalian sleep/wake regulator is hypocretin/orexin (Hcrt), whose loss results in the sleep disorder narcolepsy and that has also been implicated in feeding behavior, energy homeostasis, thermoregulation, reward seeking, addiction, and maternal behavior. Here we report that the expression pattern and axonal projections of embryonic and larval zebrafish Hcrt neurons are strikingly similar to those in mammals. We show that zebrafish larvae exhibit robust locomotive sleep/wake behaviors as early as the fifth day of development and that Hcrt overexpression promotes and consolidates wakefulness and inhibits rest. Similar to humans with insomnia, Hcrt-overexpressing larvae are hyperaroused and have dramatically reduced abilities to initiate and maintain rest at night. Remarkably, Hcrt function is modulated by but does not require normal circadian oscillations in locomotor activity. Our zebrafish model of Hcrt overexpression indicates that the ancestral function of Hcrt is to promote locomotion and inhibit rest and will facilitate the discovery of neural circuits, genes, and drugs that regulate Hcrt function and sleep.
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PMID:Hypocretin/orexin overexpression induces an insomnia-like phenotype in zebrafish. 1718 91

Melatonin, a chronobiotic that participates in the control of the circadian system, is known for its sleep-promoting effects, which include shortening of sleep latency and lengthening of sleep duration. As a result of its short half-life, melatonin does not exhibit undesirable side effects, and its broad applicability for a variety of sleep problems has been the focus of numerous scientific studies. Melatonin has not, however, received regulatory approval from the US FDA as a drug, because it can be sold freely as a food supplement. Consequently, there has been an active search for patentable melatonin receptor ligands in recent years. Ramelteon, an agonist that acts solely on melatonin MT(1) and MT(2) receptors, is of particular interest, and preliminary research indicates that it holds considerable promise for clinical applications. Ramelteon has been shown to induce sleep initiation and maintenance in various animal models and in clinical trials. In chronic insomnia, ramelteon decreases sleep latency and increases total sleep time and sleep efficiency, without causing hangover, addiction or withdrawal effects. Ramelteon is thought to promote sleep by influencing homeostatic sleep signaling mediated by the suprachiasmatic nucleus. Although ramelteon's metabolism and pharmacokinetics differ from those of melatonin, its safety seems to be sufficient for short-term application. Its long-term effects remain to be determined.
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PMID:Drug Insight: the use of melatonergic agonists for the treatment of insomnia-focus on ramelteon. 1741 Jan 9

Tobacco smoking remains a significant health problem in the United States. It has been associated with staggering morbidity and mortality, specifically due to malignancies and cardiovascular disease. Smoking cessation can be difficult and frequently requires pharmacologic interventions in addition to nonpharmacologic measures. Previously available agents are nicotine replacement products and bupropion, which increased quit rates by about 2-fold compared with placebo. Varenicline is the first drug in a new class known as the selective alpha4beta2 nicotinic receptor partial agonists. In several randomized, double-blind, 52-week clinical trials involving healthy chronic smokers, varenicline demonstrated superiority to placebo and bupropion in terms of efficacy measures. Additionally, it improved tobacco withdrawal symptoms and reinforcing effects of smoking in relapsed patients. Patients should start therapy in combination with tobacco cessation counseling 1 week before quit date and continue the regimen for 12 weeks. The dose of varenicline should be titrated to minimize nausea. The recommended dosage is 0.5 mg once daily (QD) on days 1-3; titrate to 0.5 mg twice daily (BID) on days 4-7; and 1 mg BID starting on day 8. An additional 12-week maintenance therapy may be considered for those who achieve abstinence. The most common side effects are nausea (30%), insomnia (18%), headache (15%), abnormal dreams (13%), constipation (8%), and abdominal pain (7%). Overall, varenicline is a breakthrough in the management of tobacco addiction and has demonstrated good efficacy in motivated quitters. It also provides an option for smokers who cannot tolerate other pharmacologic interventions.
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PMID:Varenicline: a selective alpha4beta2 nicotinic acetylcholine receptor partial agonist approved for smoking cessation. 1743 82

Insomnia is a subjective complaint relating to approximately 30% of the adult population in France, described by the patient as a difficulty of initiating and/or maintaining sleep. Its prevalence increases with age and sex: women are more affected than men (24% vs 14%). Insomnia is either occasional (20%), or chronic (10%). Chronic insomnia has an important impact on patients' everyday life e.g. fatigue, perturbed diurnal waking state, impaired quality-of-life... which results in lower work productivity and drowsiness as well as relational difficulties, absenteeism. About 80% of patients consult their general practitioner first. The aim of a hypnotic agent is to obtain sleep as physiological as possible. Benzodiazepines and benzodiazepines-like agents (zopiclone, zolpidem, zaleplon) are the most widely used hypnotics. However, their indications must be limited to occasional insomnia with a limited duration: less than four weeks. There is no advantage with using a combination of hypnotic agents, a practice which should be prohibited. Adverse effects can be serious, e.g. diurnal somnolence associated with risks of road accidents and, in the elderly, the risk of falls. After chronic use, hypnotics can be addictive, as their effects wear off in three to four weeks. After withdrawal, insomnia rebound is frequent. Use of hypnotics in association with alcohol is a well-known drug-addiction behavior. According to the French health insurance fund, 9% of the general population use hypnotics and about half of them regularly. Insurance refunds for hypnotics and sedatives reach more than 110 million euros annually. The efficiency of hypnotics wears off, quickly for benzodiazepines (three - four weeks), or less quickly for zopiclone and zolpidem (a few months). Insomnia is a major public health issue, each year 10% of the incident cases of insomnia treated by hypnotics joint the group of subjects with chronic insomnia. This failure to treat insomnia properly can be explained, at least in part, by several insufficiencies: physicians and pharmacists training, medical profession awareness, research, public information on the rules of good sleep (public health campaigns, booklets, role of physicians and the pharmacists).
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PMID:[Sleep disorders and hypnotic agents: medical, social and economical impact]. 1765 91

Sleep disorders, mainly insomnia and daytime somnolence, can arise from very different causes. For example insomnia may be related to anxiety-depression or occur in response to a stressful lifestyle or as an element of restless leg syndrome. Subjects with hypersomnia may present episodes of sleep apnea, drug-related depression or narcolepsia. Specific management is required for each etiology. Misuse of sleep drugs generally results from an insufficient etiological diagnosis and a misunderstanding of their proper use. These drugs can be used as necessary expedients but cannot replace correct management or treatment of the cause or causes of the sleep disorder. We present here a review of the undesirable effects, particularly among the elderly population, and of the risk of addiction to the different drugs used to induce sleep in order to propose prescription guidelines.
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PMID:[Misuse of sleep and wakefulness drugs: from undesirable effects to addiction]. 1765 95

Sedative-hypnotic medications, including benzodiazepines and non-benzodiazepines, are usually prescribed for the insomniac patients; however, the addiction, dependence and adverse effects of those medications have drawn much attention. In contrast, suanzaorentang, a traditional Chinese herb remedy, has been efficiently used for insomnia relief in China, although its mechanism remains unclear. This study was designed to further elucidate the underlying mechanism of suanzaorentang on sleep regulation. One ingredient of suanzaorentang, zizyphi spinosi semen, exhibits binding affinity for serotonin (5-hydroxytryptamine, 5-HT) receptors, 5-HT(1A) and 5-HT(2), and for GABA receptors. Our previous results have implicated that GABA(A) receptors, but not GABA(B), mediate suanzaorentang-induced sleep alteration. In current study we further elucidated the involvement of serotonin. We found that high dose of suanzaorentang (4 g/kg/2 ml) significantly increased non-rapid eye movement sleep (NREMS) when comparing to that obtained after administering starch placebo, although placebo at dose of 4 g/kg also enhanced NREMS comparing with that obtained from baseline recording. Rapid eye movement sleep (REMS) was not altered. Administration of either 5-HT(1A) antagonist (NAN-190), 5-HT(2) antagonist (ketanserin) or 5-HT(3 )antagonist (3-(4-Allylpiperazin-1-yl)-2-quinoxalinecarbonitrile) blocked suanzaorentang-induced NREMS increase. These results implicate the hypnotic effect of suanzaorentang and its effects may be mediated through serotonergic activation, in addition to GABAergic system.
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PMID:The involvement of serotonin receptors in suanzaorentang-induced sleep alteration. 1765 85

Sleep disturbances are extremely common in the early stages of recovery from alcohol dependence and may persist for several months despite continued abstinence. Studies indicate that sleep disturbances independently increase the risk for relapse to alcohol, suggesting that targeting these problems during recovery may support continued abstinence. However, there is limited information in the addiction literature about available and effective treatments for sleep disturbances in recovering alcoholic patients. The primary goals of this article are to describe the phenomenology of sleep disturbances during recovery from alcohol dependence, to outline the evidence linking sleep problems with alcohol relapse, and to describe available pharmacological and nonpharmacological treatment options, including the evidence regarding their efficacy in recovering alcoholic patients. Recommendations for future research are provided along with special considerations for treating insomnia in this population, including avoiding cross-dependent sedatives, such as benzodiazepines and benzodiazepine receptor agonists (BzRAs).
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PMID:Treatment options for sleep disturbances during alcohol recovery. 1803 31

Insomnia affects a large percentage of the population, particularly the elderly. Literature reports varying estimates of prevalence, a variation that relates to the lack of definition and consistency in diagnostic criteria. Primary insomnia (not caused by known physical/mental conditions) responds to pharmacologic therapy, while secondary insomnia(resulting from other illnesses, medications, or sleep disorders) responds to pharmacologic and psychologic treatments (cognitive therapy, relaxation techniques, stimulus control). Use of certain agents in the elderly and patients with abuse/addiction potential is a concern. Medicare Part D does not cover benzodiazepines (classified as controlled substances). Nonprescription agents are affordable but have sedation and anticholinergic side effects. Medication use should be considered a possible contributing factor. Insomnia patients experience significantly more limited activity and higher total health services than those without insomnia. Annual costs are between $92.5 billion and $107.5 billion. A standard definition and better pathways to recognize and treat insomnia are needed.
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PMID:Current landscape of insomnia in managed care. 1804 70

3-9% of schoolchildren in the U.K. suffer Attention Deficit and Hyperactivity Disorder (ADHD). Since the 1950s stimulants have been used. particularly methylphenidate and dextroamphetamine, with some 75% response rate. The first non-stimulant medication--atmoxetine hydrochloride, has also been used. However, side effects have included: growth retardation; appetite loss: headache: stomachache: heart problem: insomnia: seizure; change of character: addiction or even suicidal thoughts. Alternative treatments have been used including omega-3s, yet the way they benefit in ADHD is uncertain. They may be important in remodelling dendrites and synapses, and/or sustaining: blood brain barrier, neuronal membrane. neurotransmitter channel, receptors and ion channel. Stevens in 2003 found long-chain polyunsaturated fatty acids (LCPUFAs) effective for oppositional defiant disorder, whereas Eicosapentaenoic acid (EPA) specifically was helpful with disruptive behaviour. Docosahexaenoic acid (DHA) is important during gestation and early infancy, particularly for neurodevelopment. The Durham Trial by Richardson published in 2005, tested omega-3s with omega-6s on schoolchildren with developmental coordination disorder (many of them had ADHD symptoms), improving scores in co-ordination and short term memory.
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PMID:Attention deficit disorders--drugs or nutrition? 1830 64

Adolescents have high rates of sleep disorders and substance abuse, both of which have been associated with deleterious effects on mood, attention, and behavior. This article reviews data on the prevalence of sleep disorders, substance abuse problems, and comorbid psychiatric conditions in the adolescent population. Studies have consistently demonstrated that the prevalence of sleep problems is under-reported in adolescents in both clinical and community samples. The bidirectional correlation between substance use and sleep disturbances is also discussed. Based on the findings presented here, the authors conclude that it is imperative to improve the detection and treatment of sleep problems in children and adolescents. By treating sleep disturbances and targeting poor sleepers with additional counseling and education regarding the risk of substance use, clinicians may be able to prevent or delay the adverse effects of addiction. At the very least, the presence of insomnia should alert clinicians to the need for further evaluation for drug and alcohol abuse.
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PMID:Adolescents with insomnia and substance abuse: consequences and comorbidities. 1852 Jul 83


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