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)

(1) In the United States melatonin is just a dietary supplement, but in Europe its status varies from country to country and also over time. It is illegal in some European member states but tolerated or authorised as a drug or dietary product elsewhere. Melatonin, a hormone secreted by the pineal gland, has been on the front cover of magazines throughout the world for its claimed effects on ageing, cancer and many other health problems, opening up a vast potential market. (2) Only its use in jet lag, sleep disorders and advanced cancer has been tested clinically (albeit scantily). (3) Melatonin seems to alleviate jet lag symptoms, but that could be linked to its moderate hypnotic effect. (4) The use of melatonin to treat major insomnia cannot be envisaged until its long-term safety has been proven. With this proviso, and if efficacy is confirmed in sufficiently large comparative trials, melatonin could prove useful for treating major sleep disorders in some patients, especially blind people and those with severe neurological disabilities. (5) According to open trials conducted by a single team, melatonin, alone or combined with interleukin-2, could slightly lengthen the survival of patients with some advanced cancers, but even partial tumour remissions are rare. (6) All other "indications" are based on simplistic hypotheses or purely commercial considerations.
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PMID:Melatonin: interesting, but not miraculous. 1084 53

Melatonin is a hormone produced mainly in the pineal gland. Plasma levels exhibit a circadian variation with the highest concentration occurring at night. The human biologic effects of melatonin depend upon the time of day it is made available. One of these effects is the setting and resetting of circadian clocks (chronobiotic effect). Additionally, it may be a potent antioxidant and immunomodulator and has been shown to have antitumor, anticytokine, anti-insomnia, and anticachexia effects. Melatonin has also been shown to improve survival and performance status in patients with advanced cancer. Objective tumor response occurs with melatonin alone or when combined with interleukin-2 (IL-2). Further, melatonin reduces radiation- and chemotherapeutic-induced toxicity. Symptomatic and circadian disruption is linked to increased cancer risk. The chronobiotic capacity of melatonin to reset circadian clocks may provide a verifiable strategy to reduce cancer risk and enhance quality of life by diminishing cancer-induced circadian disruption.
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PMID:The therapeutic application of melatonin in supportive care and palliative medicine. 1608 17

Ramelton is a medication recently approved by the FDA for treatment of insomnia. Ramelton is an analogue of melatonin with a higher affinity even than that of the natural ligand. Clinically this potentially strong effect of the ligand is blunted by the fact that upon oral ingestion there is first pass metabolism of greater than 95%. This liver metabolism is mediated by the CYP1A2 enzyme. It turns out that the medication fluvoxamine approved by the FDA for the treatment of obsessive compulsive disorder is a potent inhibitor of the CYP1A2 enzyme, with the effect that co-administration of ramelton and fluvoxamine increases blood levels of ramelton by 100-200 fold. It turns out that lymphocytes bear the melatnonin receptors and stimulation of these receptors on lymphocytes cause the lymphocytes to elaborate the pro-inflammatory cytokine interleukin-2 (Il-2). Thus, here we point out that co-administration of ramelton and modest doses of fluvoxamine may be able to smoothly produce increased levels of Il-2, this may be useful in diseases and conditions such as metastatic cancer and maintenance of suppression of the HIV virus.
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PMID:Co-administration of ramelton and fluvoxamine to increase levels of interleukin-2. 1689 13

This chapter includes the aspects of melatonin. The drug is synthesized in the pineal gland starting from tryptophane or synthetically by using indole as starting material. Melatonin has been used as an adjunct to interleukin-2 therapy for malignant neoplasms, as contraceptive, in the management of various forms of insomnia, to alleviate jet lag following long flights, and finally as free radical scavenger and hence as an antioxidant and an anti-inflammatory. The chapter discusses the drug metabolism and pharmacokinetics and presents various method of analysis of this drug such as biological analysis, spectroscopic analysis, and chromatographic techniques of separation. It also discusses its physical properties such as solubility characteristics, X-ray powder diffraction pattern, and thermal methods of analysis. The chapter is concluded with a discussion on its biological properties such as activity, toxicity, and safety.
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PMID:Melatonin: comprehensive profile. 2366 5

The impressive but sad list of over forty clinical studies using various cytotoxic chemotherapies published in the last few years has failed to increase median survival of glioblastoma beyond two years after diagnosis. In view of this apparent brick wall, adjunctive non-cytotoxic growth factor blocking drugs are being tried, as in the CUSP9* protocol. A related theme is searching for agonists at growth inhibiting receptors. One such dataset is that of melatonin agonism at M1 or M2 receptors found on glioblastoma cells, being a negative regulator of these cells' growth. Melatonin itself is an endogenous hormone, but when used as an exogenously administered drug it has many disadvantages. Agomelatine, marketed as an antidepressant, and ramelteon, marketed as a treatment for insomnia, are currently-available melatonin receptor agonists. These melatonin receptor agonists have significant advantages over the natural ligand: longer half-life, better oral absorption, and higher affinity to melatonin receptors. They have an eminently benign side effect profile. As full agonists they should function to inhibit glioblastoma growth, as demonstrated for melatonin. A potentially helpful ancillary attribute of melatonergic agonists in glioblastoma treatment is an increase in interleukin-2 synthesis, expected, at least partially, to reverse some of the immunosuppression associated with glioblastoma.
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PMID:Agomelatine or ramelteon as treatment adjuncts in glioblastoma and other M1- or M2-expressing cancers. 2603 96