Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ramelteon, approved in the US for the treatment of insomnia characterised by difficulty with sleep onset, is a highly selective agonist for the melatonin MT1/MT2 receptors, which are believed to mediate the circadian rhythm in mammals. Ramelteon has negligible affinity for the MT3 binding sites and other receptors in the brain, including the opiate, dopamine, benzodiazepine and serotonin receptors, which may explain the lack of significant adverse events and lack of abuse or dependence potential observed with ramelteon. In three clinical trials in patients with chronic insomnia, ramelteon 8mg was effective in reducing sleep latency, without being associated with any significant or clinically relevant residual effects. It also generally increased total sleep time and, where assessed, sleep efficiency. In a first-night-effect model of transient insomnia, ramelteon 8mg was significantly more effective than placebo at reducing sleep latency and increasing total sleep time. Ramelteon was generally well tolerated; the most commonly reported adverse events occurring in more ramelteon than placebo recipients were somnolence (5% vs 3%), fatigue (4% vs 2%) and dizziness (5% vs 3%). Adverse events were mostly mild or moderate in nature. Ramelteon has been shown to have no potential for abuse or dependence.
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PMID:Ramelteon. 1633 46

Each year millions of travelers undertake long distance flights over one or more continents. These multiple time zone flights produce a constellation of symptoms known as jet lag. Familiar to almost every intercontinental traveler is the experience of fatigue upon arrival in a new time zone, but almost as problematic are a number of other jet lag symptoms. These include reduced alertness, nighttime insomnia, loss of appetite, depressed mood, poor psychomotor coordination and reduced cognitive skills, all symptoms which are closely affected by both the length and direction of travel. The most important jet lag symptoms are due to disruptions to the body's sleep/wake cycle. Clinical and pathophysiological studies also indicate that jet lag can exacerbate existing affective disorders. It has been suggested that dysregulation of melatonin secretion and occurrence of circadian rhythm disturbances may be the common links which underlie jet lag and affective disorders. Largely because of its regulatory effects on the circadian system, melatonin has proven to be highly effective for treating the range of symptoms that accompany transmeridian air travel. Additionally, it has been found to be of value in treating mood disorders like seasonal affective disorder. Melatonin acts on MT(1) and MT(2) melatonin receptors located in the hypothalamic suprachiasmatic nuclei, the site of the body's master circadian clock. Melatonin resets disturbed circadian rhythms and promotes sleep in jet lag and other circadian rhythm sleep disorders, including delayed sleep phase syndrome and shift-work disorder. Although post-flight melatonin administration works efficiently in transmeridian flights across less than 7-8 times zones, in the case longer distances, melatonin should be given by 2-3 days in advance to the flight. To deal with the unwanted side effects which usually accompany this pre-departure treatment (acute soporific and sedative effects in times that may not be wanted), the suppression of circadian rhythmicity by covering symmetrically the phase delay and the phase advance portions of the phase response curve for light, together with the administration of melatonin at local bedtime to resynchronize the circadian oscillator, have been proposed. The current view that sleep loss is a major cause of jet lag has focused interest on two recently developed pharmacological agents. Ramelteon and agomelatine are melatonin receptor agonists which, compared to melatonin itself, have a longer half-life and greater affinity for melatonin receptors and consequently are thought to hold promise for treating a variety of circadian disruptions.
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PMID:Jet lag: therapeutic use of melatonin and possible application of melatonin analogs. 1834 69