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)

Melatonin is sold in the United States as a dietary supplement and is promoted primarily as an aid for insomnia, stress, jet lag, and aging. Cases of acute poisoning have not been reported, partially because of problems in assessment of toxicity. We report the case of a 66-year-old man who became lethargic and disoriented after taking 24 mg melatonin to aid relaxation and sleep the evening before prostate surgery. He recovered uneventfully, and after the scheduled surgery he resumed his regular practice of taking 6 mg melatonin with prescription sedative drugs. Although melatonin is not regulated as a drug, it may interact with benzodiazepines, be antagonized by naloxone and flumazenil, and interact with melatonin receptors in the central nervous system and elsewhere in the body. Melatonin appears to be pharmacologically active and should not be considered a benign agent on overdose.
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PMID:Problems in assessment of acute melatonin overdose. 911 43

Melatonin, a hormone produced by the pineal gland, appears to help regulate the sleep-wake cycle. With further study and clinical experience, it may become an accepted therapy for insomnia. Although melatonin preparations are available without prescription in health food stores and pharmacies, their potency, purity, safety and effectiveness cannot be assured. Until large clinical trials provide further information about melatonin's efficacy, adverse effects, drug interactions and effects on various disease states, melatonin products should be used with the understanding that many questions about their safety remain unanswered.
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PMID:Melatonin. 993 Jan 25

Melatonin is a neuroendocrine hormone which is currently receiving considerable attention as a treatment for jet lag, a treatment for insomnia and, by some, a possible "magic bullet" for delaying the effects of aging and preventing cancer. Production of melatonin is focused primarily in the pineal gland with very wide daily shifts in production controlled by the day/night cycle. The potential for increased disease as a consequence of lower or higher than average production of this hormone has not been well studied, although potential environmental agents may modulate circulating levels (e.g., electric and magnetic fields). In this manuscript, a physiologically realistic mathematical model for the production, distribution, and metabolism of melatonin is developed as a precursor to a future study of the role of chemicals and environmental agents in altering this system. Values for key aspects of the system (e.g., diurnal rates of production of the hormone in the pineal gland) were obtained from the literature and the model was validated against data on circulating levels. The mathematical equations and model parameters are presented.
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PMID:A mathematical model of production, distribution, and metabolism of melatonin in mammalian systems. 935 10

Melatonin is a hormone produced by the pineal gland mainly during the night. Its primary function is to coordinate biological rhythms. It may be used for therapy of chronobiological disorders, such as occur in jet lag, shift work, blind persons or in specific forms of insomnia. Due to its anti-gonadotropic effect, melatonin in high doses has been used as a contraceptive. In-vitro and animal studies have demonstrated cancer inhibition, immun-stimulating and rejuvenating effects, but none of these claims have been confirmed in clinical studies. Melatonin used over a short period is not associated with significant side-effects, but the tolerability of long-term administration is unknown. As the products are not always of pharmaceutical quality, one should avoid uncontrolled use of melatonin.
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PMID:[Melatonin--clinical perspectives in prevention and therapy]. 938 20

Although the causes are different, totally blind people (without light perception) and night shift workers have in common recurrent bouts of insomnia and wake-time sleepiness that occur when their preferred (or mandated) sleep and wake times are out of synchrony with their endogenous circadian rhythms. In this article, the patterns of circadian desynchrony in these two populations are briefly reviewed with special emphasis on longitudinal studies in individual subjects that used the timing of melatonin secretion as a circadian marker. In totally blind people, the most commonly observed pattern is a free-running rhythm with a stable non-24-h circadian period (24.2-24.5 h), although some subjectively blind people are normally entrained, perhaps by residually intact retinoypothalamic photic pathways. Experiments at the cellular and behavioral levels have shown that melatonin can produce time dependent circadian phase shifts. With this in mind, melatonin has been administered to blind people in an attempt to entrain abnormal circadian rhythms, and substantial phase shifts have been accomplished; however, it remains to be demonstrated unequivocally that normal long-term entrainment can be produced. In untreated night shift workers, the degree and direction of phase shifting in response to an inverted sleep-wake schedule appears to be quite variable. When given at the optimal circadian time, melatonin treatment appears to facilitate phase shifting in the desired direction. Melatonin given prior to a night worker's daytime sleep also may attenuate interference from the circadian alerting process. Because melatonin has both phase-shifting and sleep-promoting actions, night shift workers, who number in the millions, may be the most likely group to benefit from treatment.
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PMID:Melatonin as a chronobiotic: treatment of circadian desynchrony in night workers and the blind. 940 35

Despite the fact that melatonin has been released for public use in the United States by the Food and Drug Administration and is available over the counter nationwide, there currently is a total lack of information on the toxicology of melatonin. In Europe, melatonin has a completely different status in that it is considered a "neurohormone" and cannot be sold over the counter. Even though administration of melatonin in humans, as well as in animals (even at supraphysiological doses), has not shown evidence of toxicological effects (i.e., no deaths), a drug toxicological file still would need to be prepared and approved by the regulatory authorities. Several features that are specific to this neurohormone need to be taken into consideration. Whatever the species concerned, melatonin is secreted during the night; it is the "hormone of darkness." It presents a circadian rhythm and a circannual rhythm (in photoperiodic species). The duration of these secretions could have an impact on the reproductive system, for example, showing the importance of the pharmacodynamics of melatonin. An inappropriate time schedule of melatonin administration could induce supraphysiological concentrations of the neurohormone and a desensitization of melatonin receptors. A long duration of exposure to melatonin also could mimic an "artificial darkness" condition when a circadian rhythm with a basal zero level during the day needs to be conserved for a physiological function. Furthermore, administration of large doses of melatonin could induce high concentrations of melatonin and of different metabolites that could have deleterious effects per se. Numerous books, magazines, and articles have praised melatonin as a "miraculous cure-all" for ailments ranging from sleeplessness, to aging, without any clinical evidence of efficacy (with the exception of its chronobiotic and resynchronizing effect). Very little attention has been paid to the possible side effects of melatonin. Nightmares, hypotension, sleep disorders, abdominal pain, etcetera, have been reported. In fact, analysis of the known pharmacological profile of melatonin and/or of its metabolites, based on scientific preclinical studies, constitutes a basis for prediction of adverse drug reactions or side effects. These include (1) the central nervous system, (2) the cardiovascular system and platelet aggregation, (3) glucose metabolism, (4) immunology, and (5) cancer. The knowledge of the fundamental mechanism of action of melatonin, including molecular biology, also needs to be taken into account for evaluation of possible side effects. Two types of melatonin receptors have been cloned (related to cyclic AMP), and the possibility of intracellular action of melatonin cannot be excluded. Melatonin receptors are present in the periphery and also at the level of the central nervous system, particularly on the suprachiasmatic nucleus that "drives" a circadian rhythm to many other areas on which it projects. Among those, the hypothalamus (which has melatonin receptors) plays a fundamental role in the hormonal homeostasis and modulation control of the organism. Special preclinical and pharmacological studies that take into account all these parameters need to be designed for safety evaluation and risk assessment of this specific neurohormone.
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PMID:Toxicology of melatonin. 940 48

Melatonin is a neurohormone produced by the human pineal gland that plays a role in the regulation of many physiologic processes and has been proposed as a therapy for everything from insomnia to metastatic carcinoma. Melatonin is available in the United States without prescription, and adverse effects appear to be uncommon. However, because melatonin appears to have immunomodulatory properties, the potential exists for the development of autoimmune-related side effects. We describe a patient in whom characteristic clinical and laboratory features of autoimmune hepatitis developed after beginning melatonin therapy for the treatment of insomnia. Liver biopsy demonstrated histologic features of autoimmune hepatitis. Rapid symptomatic and biochemical improvement resulted from the initiation of immunosuppressive therapy; however, hepatitis recurred after the withdrawal of steroid therapy. The temporal relation observed between melatonin use and the development of autoimmune hepatitis raises the possibility that the drug might be involved in the pathogenesis of this patient's autoimmune disease.
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PMID:Is melatonin associated with the development of autoimmune hepatitis? 941 27

Long-haul flights allow rapid crossing of times zones. When four time zones are crossed, the transmeridian flight induce jet-lag syndrome. Jet-lag is essentially composed of digestive and behavioural disturbances (insomnia and/or drowsiness). It is due to an immediate conflict between external time cues, which have been phase-advanced or phase-delayed by eastward or westward flight, respectively, and the endogenous clock. This conflict induces a desynchronization of the biological rhythms. Different counter-measures could be advised, but the most used is the pharmacological one. Hypnotics like benzodiazepines, cyclopyrones or imidazopyridines induce a recovery sleep but could also induce secondary effects in case of chronic use. Melatonin secreted by pineal gland needs more studies before a safety use for jet-lag treatment. Psychostimulants are able to induce a prolonged wakefulness. But amphetamine-like substances have to be forbidden because of the importance of side effects. New researches are studying a new galenic form of caffeine: the time release caffeine, which permits to induce a long and good quality wakefulness.
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PMID:[Role of the pharmacopoeia in the prevention of jet-lag]. 947 72

Melatonin has been shown to have hypnotic and hypothermic effects in young adults and has been proposed as treatment for insomnia. However, the hypnotic and thermoregulatory effects of melatonin remain to be simultaneously investigated for aged good and poor sleepers. The aim of this study was to explore the short-term effects of exogenous oral daytime melatonin on core body temperature, sleep latency, and subjective vigor and affect in aged women. Twelve sleep maintenance insomniacs and 10 good sleeping postmenopausal female subjects [mean (SD) age = 65.2 (7.4) years] participated in a double-blind, crossover study in which they received a capsule containing either melatonin (5 mg) or a placebo at 1400 hours. Continuous core body temperature and hourly multiple sleep latency tests (MSLT) were collected from 1100-2030 hours. Self-reported estimates of global vigor (sleepiness) and affect were collected prior to each MSLT using visual analog scales. Comparison of good and poor sleepers failed to reveal any significant differences in core body temperature, sleep latency, or subjective vigor and affect. However, for both groups combined, melatonin administration [absolute postadministration mean (SEM) = 36.9 (0.05) degrees C] significantly lowered core body temperature compared with placebo [37.1 (0.05) degrees C]. Similarly, melatonin administration significantly reduced latency to stage 1 (SOL1) and stage 2 (SOL2) [absolute postadministration mean SOL1 = 20.1 (1.7) and SOL2 = 20.7 (1.6) minutes] compared with placebo [SOL1 = 24.3 (1.2) and SOL2 = 25.2 (1.1) minutes]. Treatment had no significant effect on either vigor or affect. Overall, our results suggest that although short-term exogenous oral daytime melatonin has significant hypothermic and hypnotic effects in aged women, the size of the effects is modest.
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PMID:Daytime melatonin administration in elderly good and poor sleepers: effects on core body temperature and sleep latency. 949 23

Melatonin (MLT) is a methoxyindole secreted principally by the pineal gland. It is synthesized at night under normal environmental conditions. The endogenous rhythm of secretion is generated by the suprachiasmatic nuclei and entrained by the light/dark cycle. Light is able to both suppress or entrain MLT production on light schedule. The nyctohemeral rhythm of this hormone can be determined by repeated measurement of plasma or saliva MLT or urine sulfatoxy-MLT, the main hepatic metabolite. MLT can be considered as the output (the hand) of the endogenous clock. Since the regulating system follows a central and sympathetic nervous pathway, an abnormality at any level could unspecifically modify the MLT secretion, especially in patients with sympathalgia or dysautonomia. MLT plays the role of an endogenous zeitgeber on core temperature or sleep-wake cycle. Exogenous MLT is able to influence the endogenous secretion of the hormone according to a phase-response curve. There are practical implications for this property in situations when biological rhythms are disturbed (jet-lag syndrome, delayed sleep phase syndrome, insomnia in blind people, shift-work, insomnia in elderly people). Improvement of pharmaceutical forms (controlled release preparations) or development of MLT analogs could lead to decisive progress.
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PMID:The physiology and pharmacology of melatonin in humans. 955 Jan 14


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