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Insomnia
Published in Charles Theisler, Adjuvant Medical Care, 2023
Melatonin is a hormone released by the pineal gland. This hormone helps regulate sleep patterns. Low levels of melatonin can cause insomnia. Melatonin has little dependence potential, is not associated with habituation, and typically produces no hangover. There is no evidence of patients developing a tolerance to melatonin. Melatonin can provide meaningful improvements in sleep quality, morning alertness, and sleep onset latency.4,5
Sleep and Women's Health
Published in Michelle Tollefson, Nancy Eriksen, Neha Pathak, Improving Women's Health Across the Lifespan, 2021
Melatonin may be considered in adolescents with insomnia or an evening chronotype, with regular follow-up. There is a lack of consistency in dosing guidelines: the Canadian Pediatric Society recommends 5 mg of melatonin 30–60 minutes before bed.100 An encouraging long-term follow-up study in prepubertal children who started melatonin for chronic sleep onset insomnia not responsive to sleep hygiene measures found that after 7–10 years, 75% had normal sleep without medications. The other 25% who continued melatonin had improved sleep quality and no significant adverse effects.101 Since melatonin is regulated as a dietary supplement, finding a good-quality brand is essential.
Emerging Highlights on Natural Prodrug Molecules with Multifarious Therapeutic Perspectives
Published in Debarshi Kar Mahapatra, Cristóbal Noé Aguilar, A. K. Haghi, Applied Pharmaceutical Practice and Nutraceuticals, 2021
Mojabir Hussen Ansari, Vaibhav Shende, Debarshi Kar Mahapatra
Melatonin (5-methoxy-N-acetyltryptamine) was first discovered by Aaron Lerner in the year 1958 from bovine pineal. Retina, platelets, bone marrow cells, lymphocytes, skin, Harderian gland, gastrointestinal tract, cerebellum, etc., are also reported as a source of extrapineal supply of melatonin. Melatonin is mainly prepared by the pinealocytes from an essential amino acid tryptophan. Tryptophan is synthesized by hydroxylation of 5-hydroxytryptophan by the enzyme tryptophan-5-hydroxylase then further changed into decarboxylated form with the aid of the 5-hydroxytryptophan decarboxylase enzyme. The synthesis and secretion of melatonin are enhanced by the way of darkness and inhibited by the way of light.13 Melatonin is an omnipresent molecule having natural and powerful antioxidant proprieties and it is safe when administered exogenously. Melatonin also possesses potential anti-inflammatory effects due to inhibiting inflammasome activation. Melatonin also owns its anti-apoptotic activities particularly by inhibiting Caspase-3 cleavage and mPTP opening. The presence and the inter-distance of 5-methoxy group and the N-acetyl chain are the two critical factors in the determination of specificity and amphiphilicity of melatonin.14 Scientific studies on MT1 and MT2 receptor knockout mice have resulted that MT1 and MT2 receptors play specific roles in sleep. Melatonin and melatonin agonists also play essential roles in the remedy of insomnia by activating MT1 and MT2 melatonin receptors.15
The role of vitamin D deficiency in the development of paediatric diseases
Published in Annals of Medicine, 2023
Zhu Liu, Shiming Huang, Xiaoli Yuan, Yan Wang, Yannan Liu, Jing Zhou
Melatonin is an indoleamine produced by the pineal gland mostly found in the suprachiasmatic nucleus of the hypothalamus and the cerebrospinal fluid. Melatonin is essential for regulating sleep/wake cycles and biological rhythms [46]. According to literature, the prevalence of sleep disorders in ASD children ranged from 40 to 93%, as recently reported by Petruzzelli MG [47]. Melatonin is clinically used to treat sleep disorders. In the clinical trial, 104 weeks of melatonin therapy were administered to ASD children and adolescents. Melatonin therapy significantly improved their sleep disorders and sleep quality [48]. Researchers proposed that VitD inhibited serotonin production by regulating melatonin levels outside the blood-brain barrier [49]. In the evening, the levels of 25(OH)D and 1,25(OH)2D in serum and peripheral TPH1 gene expression increased, which stimulated melatonin production [50]. ASD children with sleeping issues may benefit from low-dose melatonin due to its addictive properties. Therefore, it is still necessary to investigate the effects of melatonin combined with VitD in treating ASD children on sleeping problems.
Understanding the role of chronopharmacology for drug optimization: what do we know?
Published in Expert Review of Clinical Pharmacology, 2023
Akio Fujimura, Kentaro Ushijima
Disruption of the circadian clock by travel across time zones can cause jet lag, which is one of the exogenous circadian rhythm sleep-wake disorders. Melatonin agonists are available for the treatment of insomnia characterized by difficulty with sleep onset in patients with jet lag [101]. In one study, subjects with a history of jet lag-induced sleep difficulty were allocated to receive ramelteon, a MT1, MT2, and MT3 agonist, at doses of 1, 4 or 8 mg or to receive placebo [102]. Ramelteon 1 mg was found to reduce sleep latency in comparison with placebo. In another study, healthy subjects with experimentally induced jet lag were allocated to receive tasimelteon, a MT1 and MT2 agonist, at a dose of 20, 50 or 100 mg or to receive placebo [103]. All doses of the drug significantly reduced sleep latency and improved sleep efficiency. Therefore, melatonin agonists are effective for the treatment of sleep problems in subjects with jet lag.
Assessing the potential for drug interactions and long term safety of melatonin for the treatment of insomnia in children with autism spectrum disorder
Published in Expert Review of Clinical Pharmacology, 2022
Melatonin is a neuro-hormone produced by the pineal gland during nocturnal periods (production is suppressed by ambient light, predominantly blue light) under the control of the circadian clock residing at the suprachiasmatic nuclei (SCN). The circadian rhythm in melatonin serves a signal of darkness in the organism to properly time circadian sleep–wake rhythms and enhance sleepiness [8]. Melatonin is involved in the regulation of sleep in two ways: it facilitates synchronization of the circadian clock with the ambient day–night cycle (chronobiotic effect) and attenuates the wake-promoting signal of the circadian system (soporific effect) [9]. Clinically meaningful effects of melatonin treatment have been demonstrated in circadian rhythms sleep disorders (e.g. non-24 h sleep–wake rhythms in the blind, delayed sleep phase syndrome, and jet lag) and particular types of insomnia (e.g. insomnia in children with neurodevelopmental disorders and insomnia characterized by poor (non-restorative) sleep quality in the elderly) [10].