tasimelteon and Neurodegenerative-Diseases

Alzheimer's disease (AD) is an age-dependent neurodegenerative disease with progressive cognition and memory loss, insomnia, and other abnormal behavioral changes. Amongst various hypotheses for AD pathophysiology, occupational stress-induced Alzheimer's has recently been reported in many AD cases.. Studies pertaining to the same suggest that stress leads to insomnia or sleep disruption, which further leads to neuroinflammation due to oxidative stress, both of which are major harbingers of AD. Additionally, overall sleep deficit is associated with progressive cognitive and memory decline, which adds more inconvenience to Alzheimer's disease. Based on this, any triumphant AD management needs a pharmacological intervention that can not only antagonize the amyloid betainduced neurotoxicity but also correct the sleep-wake cycle disruption. Chronobiotic therapeutics like melatonin offer vital neuroprotective effects by eliciting its action through more than one of the pathologies of AD. This is also bolstered by the finding that endogenous melatonin levels are lower in AD patients. This melatonin replacement therapy can be especially useful in AD treatment, but only in the early phases of the disease and in cases where the melatonin receptors are intact and functioning.. To negate such limitations and extend the action and therapeutic efficacy of melatonin- mediated actions towards AD treatment, melatonin analogue like tasimelteon can pose a high therapeutic value in AD treatment superior to that provided by melatonin. This review encapsulates all details about how AD is believed to occur and how current situations influence it, along with how melatonin and tasimelteon act towards treating Alzheimer's.

Topics: Alzheimer Disease; Humans; Melatonin; Neurodegenerative Diseases; Sleep Initiation and Maintenance Disorders

Circadian rhythms oscillate throughout a 24-h period and impact many physiological processes and aspects of daily life, including feeding behaviors, regulation of the sleep-wake cycle, and metabolic homeostasis. Misalignment between the endogenous biological clock and exogenous light-dark cycle can cause significant distress and dysfunction, and treatment aims for resynchronization with the external clock and environment. This article begins with a brief historical context of progress in the understanding of circadian rhythms, and then provides an overview of circadian neurobiology and the endogenous molecular clock. Various tools used in the diagnosis of circadian rhythm sleep-wake disorders, including sleep diaries and actigraphy monitoring, are then discussed, as are the therapeutic applications of strategically timed light therapy, melatonin, and other behavioral and pharmacological therapies including the melatonin agonist tasimelteon. Management strategies towards each major human circadian sleep-wake rhythm disorder, as outlined in the current International Classification of Sleep Disorders - Third Edition, including jet lag and shift work disorders, delayed and advanced sleep-wake phase rhythm disorders, non-24-h sleep-wake rhythm disorder, and irregular sleep-wake rhythm disorder are summarized. Last, an overview of chronotherapies and the circadian dysregulation of neurodegenerative diseases is reviewed.

Topics: Benzofurans; Chronobiology Disorders; Circadian Rhythm; Cyclopropanes; Humans; Neurodegenerative Diseases

Several melatonin receptors agonists (ramelteon, prolonged-release melatonin, agomelatine and tasimelteon) have recently become available for the treatment of insomnia, depression and circadian rhythms sleep-wake disorders. The efficacy and safety profiles of these compounds in the treatment of the indicated disorders are reviewed. Accumulating evidence indicates that sleep-wake disorders and co-existing medical conditions are mutually exacerbating. This understanding has now been incorporated into the new Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5). Therefore, when evaluating the risk/benefit ratio of sleep drugs, it is pertinent to also evaluate their effects on wake and comorbid condition. Beneficial effects of melatonin receptor agonists on comorbid neurological, psychiatric, cardiovascular and metabolic symptomatology beyond sleep regulation are also described. The review underlines the beneficial value of enhancing physiological sleep in comorbid conditions.

Topics: Acetamides; Animals; Benzofurans; Clinical Trials as Topic; Cyclopropanes; Humans; Hypnotics and Sedatives; Indenes; Melatonin; Neurodegenerative Diseases; Receptors, Melatonin; Sleep Wake Disorders