Product

Melatonin produced in the pineal gland, which is outside of the blood-brain barrier, acts as an endocrine hormone since it is released into the blood. By contrast, melatonin produced by the retina and the gastrointestinal (GI) tract acts as a paracrine hormone.[citation needed]

Light/dark information reaches the suprachiasmatic nuclei (SCN) via retinal photosensitive ganglion cells, intrinsically photosensitive photoreceptor cells, distinct from those involved in image forming (that is, these light sensitive cells are a third type in the retina, in addition to rods and cones). These cells represent approximately 2% of the retinal ganglion cells in humans and express the photopigment melanopsin.[27] The sensitivity of melanopsin is consistent with that of a vitamin A-based photopigment with a peak sensitivity at 484 nm (blue light).[28] This photoperiod cue entrains the circadian rhythm, and the resultant production of specific "dark"- and "light"-induced neural and endocrine signals which regulate behavioral and physiological circadian rhythms. Melatonin is secreted in darkness in both day-active (diurnal) and night-active (nocturnal) animals.[8]

[edit] In humans

[edit] Circadian rhythm

In humans, melatonin is produced by the pineal gland, a gland about the size of a pea, located in the center of the brain but outside the blood-brain barrier. The melatonin signal forms part of the system that regulates the sleep-wake cycle by chemically causing drowsiness and lowering the body temperature, but it is the central nervous system (more specifically, the SCN) that controls the daily cycle in most components of the paracrine and endocrine systems[29][30] rather than the melatonin signal (as was once postulated).

Infants' melatonin levels become regular in about the third month after birth, with the highest levels measured between midnight and 08:00 (8 AM).[31]

In humans, 90% of melatonin is cleared in a single passage through the liver, a small amount is excreted in urine,[32] and a small amount is found in saliva.

[edit] Light dependence

Production of melatonin by the pineal gland is inhibited by light and permitted by darkness. For this reason melatonin has been called "the hormone of darkness". Its onset each evening is called the Dim-Light Melatonin Onset (DLMO). Secretion of melatonin as well as its level in the blood, peaks in the middle of the night, and gradually falls during the second half of the night, with normal variations in timing according to an individual's chronotype.[33] Terman et al. devised a formulation which mimics that gradual washout (vs. the spikes in blood concentration and rapid washout associated with most over-the-counter melatonin tablets). When used several hours before sleep, the compound shifts the circadian clock earlier, thus promoting earlier sleep onset and morning awakening.[34]

It is principally blue light, around 460 to 480nm, that suppresses melatonin,[35] increasingly with increased light intensity and length of exposure. Until recent history, humans in temperate climates were exposed to few hours of (blue) daylight in the winter; their fires gave predominantly yellow light. Wearing glasses that block blue light in the hours before bedtime may avoid melatonin loss. Kayumov et al. showed that light containing only wavelengths greater than 530 nm does not suppress melatonin in bright-light conditions.[36] Use of blue-blocking goggles the last hours before bedtime has also been advised for people who need to adjust to an earlier bedtime, as melatonin promotes sleepiness.

[edit] Antioxidant

Besides its function as synchronizer of the biological clock, melatonin also exerts a powerful antioxidant activity. The discovery of melatonin as an antioxidant was made in 1993.[19] In many less complex life forms, this is its only known purpose.[37] Melatonin is an antioxidant that can easily cross cell membranes and the blood-brain barrier.[6] Melatonin is a direct scavenger of OH, O2−, and NO.[38] Unlike other antioxidants, melatonin does not undergo redox cycling, the ability of a molecule to undergo reduction and oxidation repeatedly. Redox cycling may allow other antioxidants (such as vitamin C) to act as pro-oxidants, counterintuitively promoting free radical formation. Melatonin, on the other hand, once oxidized, cannot be reduced to its former state because it forms several stable end-products upon reacting with free radicals. Therefore, it has been referred to as a terminal (or suicidal) antioxidant.[39]

Recent research indicates that the first metabolite of melatonin in the melatonin antioxidant pathway may be N(1)-acetyl-N(2)-formyl-5-methoxykynuramine (or AFMK) rather than the common, excreted 6-hydroxymelatonin sulfate. AFMK alone is detectable in unicellular organisms and metazoans. A single AFMK molecule can neutralize up to 10 ROS/RNS (reactive oxygen species/reactive nitrogen species) since many of the products of the reaction/derivatives (including melatonin) are themselves antioxidants. This capacity to absorb free radicals extends at least to the quaternary metabolites of melatonin, a process referred to as "the free radical scavenging cascade". This is not true of other, conventional antioxidants.[37]

In animal models, melatonin has been demonstrated to prevent the damage to DNA by some carcinogens, stopping the mechanism by which they cause cancer.[40] It also has been found to be effective in protecting against brain injury caused by ROS release in experimental hypoxic brain damage in newborn rats.[41] Melatonin's antioxidant activity may reduce damage caused by some types of Parkinson's disease, may play a role in preventing cardiac arrhythmia and may increase longevity; it has been shown to increase the average life span of mice by 20% in some studies.[42][43][44]

[edit] Immune system

While it is known that melatonin interacts with the immune system,[45][46] the details of those interactions are unclear. There have been few trials designed to judge the effectiveness of melatonin in disease treatment. Most existing data are based on small, incomplete clinical trials. Any positive immunological effect is thought to result from melatonin acting on high affinity receptors (MT1 and MT2) expressed in immunocompetent cells. In preclinical studies, melatonin may enhance cytokine production,[47] and by doing this counteract acquired immunodeficiences. Some studies also suggest that melatonin might be useful fighting infectious disease[48] including viral, such as HIV, and bacterial infections, and potentially in the treatment of cancer.[49]

[edit] Dreaming

Some supplemental melatonin users report an increase in vivid dreaming. Extremely high doses of melatonin (50 mg) dramatically increased REM sleep time and dream activity in both people with and without narcolepsy.[52] Many psychoactive drugs, such as cannabis and lysergic acid diethylamide (LSD), increase melatonin synthesis.[52] It has been suggested that nonpolar (lipid-soluble) indolic hallucinogenic drugs emulate melatonin activity in the awakened state and that both act on the same areas of the brain.[52]

[edit] Autism

Individuals with autism spectrum disorders (ASD) may have lower than normal levels of melatonin. A 2008 study found that unaffected parents of individuals with ASD also have lower melatonin levels, and that the deficits were associated with low activity of the ASMT gene, which encodes the last enzyme of melatonin synthesis.[53]

[edit] Current and potential medical indications

[edit] Treatment of circadian rhythm disorders

Exogenous melatonin taken in the evening is, together with light therapy upon awakening, the standard treatment for delayed sleep phase syndrome (DSPS) and non-24-hour sleep-wake syndrome. It appears to have some use against other circadian rhythm sleep disorders as well, such as jet lag and the problems of people who work rotating or night shifts. Melatonin reduces sleep onset latency to a greater extent in people with DSPS than in people with insomnia.[32]

Taken 30 to 90 minutes before bedtime, melatonin supplementation acts as a mild hypnotic. It causes melatonin levels in the blood to rise earlier than the brain's own production accomplishes. This usage is now commonly used in sleep and relaxation drinks.[56]

A very small dose taken several hours before bedtime in accordance with the phase response curve for melatonin in humans (PRC) doesn't cause sleepiness but, acting as a chronobiotic (affecting aspects of biological time structure),[57] advances the phase slightly and is additive to the effect of using light therapy upon awakening. Light therapy may advance the phase about one to two-and-a-half hours and a small oral dose melatonin, timed correctly some hours before bedtime, can add about 30 minutes to the advance achieved with light therapy.[58]

[edit] Preventing ischemic damage

Melatonin has been shown to reduce tissue damage in rats due to ischemia in both the brain[59] and the heart;[60] however, this has not been tested in humans.

[edit] Learning, memory and Alzheimer's

Melatonin receptors appear to be important in mechanisms of learning and memory in mice,[61] and melatonin can alter electrophysiological processes associated with memory, such as long-term potentiation (LTP). The first published evidence that melatonin may be useful in Alzheimer's disease was the demonstration that this neurohormone prevents neuronal death caused by exposure to the amyloid beta protein, a neurotoxic substance that accumulates in the brains of patients with the disorder.[62] Melatonin also inhibits the aggregation of the amyloid beta protein into neurotoxic microaggregates which seem to underlie the neurotoxicity of this protein, causing death of neurons and formation of neurofibrillary tangles, the other neuropathological landmark of Alzheimer's disease.[63]

Melatonin has been shown to prevent the hyperphosphorylation of the tau protein in rats. Hyperphosphorylation of tau protein can also result in the formation of neurofibrillary tangles. Studies in rats suggest that melatonin may be effective for treating Alzheimer's disease.[64] These same neurofibrillary tangles can be found in the hypothalamus in patients with Alzheimer's, adversely affecting their bodies' production of melatonin. Those Alzheimer's patients with this specific affliction often show heightened afternoon agitation, called sundowning, which has been shown in many studies to be effectively treated with melatonin supplements in the evening.[65]

Delirium

A randomized placebo-controlled trial, showed that low dose (0.5 mg) melatonin supplementaion to elderly patients admitted to acute Medicine services, significantly reduced delirium.[66]

[edit] ADHD

Research shows that after melatonin is administered to ADHD patients on methylphenidate, the time needed to fall asleep is significantly reduced. Furthermore, the effects of the melatonin after three months showed no change from its effects after one week of use.[67]

[edit] Fertility

A research team in Italy has found that melatonin supplementation in the evening in perimenopausal women produces an improvement in thyroid function and gonadotropin levels, as well as restoring fertility and menstruation and preventing the depression associated with the menopause.[68] However, at the same time, some resources warn women trying to conceive not to take a melatonin supplement.[69] One study reported that three mg of melatonin taken in the evening raised prolactin levels in six out of seven women.[70] Melatonin also lowers FSH levels. It is believed that these hormonal changes could in some women impair fertility.[1]

[edit] Toxicology

Melatonin has a very low toxicity in rats. Rat maternal toxicity: the no observable adverse effect level (NOAEL) and lowest observed adverse effect level (LOAEL) were 100 and 200 mg/kg/day, respectively, and the developmental toxicity NOAEL was >= 200 mg/kg/day.[71]

[edit] Headaches

[edit] Mood disorders

Melatonin has been shown to be effective in treating one form of depression, seasonal affective disorder,[74] and is being considered for bipolar and other disorders where circadian disturbances are involved.[75] It has been observed that bipolar disorder might have, as a "trait marker" (something which is characteristic of being bipolar, that does not change with state), supersensitivity to light, i.e. a greater decrease in melatonin secretion in response to light exposure at night.[76] This could be contrasted with drug-free recovered bipolar patients not showing light hypersensitivity.[77]

[edit] Cancer

A systematic review of unblinded clinical trials involving a total of 643 cancer patients using melatonin found a reduced incidence of death.[78] Another clinical trial is due to be completed in 2012.[79] Melatonin levels at night are reduced to 50% by exposure to a low-level incandescent bulb for only 39 minutes, and it has been suspected that women with the brightest bedrooms have an increased risk for breast cancer.[80] Reduced melatonin production has been proposed as a likely factor in the significantly higher cancer rates in night workers.[81]

[edit] Gallbladder stones

Melatonin presence in the gallbladder has many protective properties, such as converting cholesterol to bile, preventing oxidative stress, and increasing the mobility of gallstones from the gallbladder.[82] It also decreases the amount of cholesterol produced in the gallbladder by regulating the cholesterol that passes through the intestinal wall. In guinea pigs, melatonin administration restored normal function by reducing inflammation after induced Cholecystitis, whether administered before or after onset of inflammation.[82] Relatively speaking, concentration of melatonin in the bile is 2–3 times higher than the otherwise very low daytime melatonin levels in the blood across many diurnal mammals, including humans.[83]

[edit] Amyotrophic lateral sclerosis

In animal models, melatonin has been shown to ameliorate glutamate-induced neuronal death, possibly due to its antioxidant effects. In a clinical safety study involving 31 ALS patients, high-dose rectal melatonin (300 mg/day for 2 years) was shown to be tolerated well.[84]

[edit] Obesity

Melatonin is involved in energy metabolism and body weight control in small animals. Many studies show that chronic melatonin supplementation in drinking water reduces body weight and abdominal fat in experimental animals, especially in the middle-aged rats.[85] Interestingly, the weight loss effect of melatonin does not require the animals to eat less and to be physically more active. A potential mechanism is that melatonin promotes the recruitment of brown adipose tissue (BAT) as well as enhances its activity.[86] This effect would raise the basal metabolic rate by stimulating thermogenesis, heat generation through uncoupling oxidative phosphorylation in mitochondria. Whether the results of animal studies can be extrapolated to human obesity is a matter of future clinical trials since substantially active BAT has been identified in adult humans.

[edit] Other

Histologically, it is believed that melatonin has some effects for sexual development in higher organisms.[87] It is involved in the seasonal timing of reproduction in rodents, at least.

Melatonin increases proliferation of cultured neural stem cells obtained from mice nervous tissue.[88]

Exogenous melatonin has also been used in a small clinical trial by Kunz D and Bes F to treat Periodic Limb Movement Disorder, a common neurological condition which, when severe, adversely affects sleep and causes excessive daytime fatigue. The sufferer is affected by mini arousals (often without noticing) during sleep when the limb movements occur in a frequent rhythmic fashion, often involving leg kicking but sometimes also involving the arms. Partners are often the first to notice the condition. In the trial, 7 out of the 9 taking part showed significant improvement.[citation needed]

A veterinarian may recommend melatonin for dogs suffering from aggression or separation anxiety.[citation needed]

[edit] Use as medication

Studies have found that the use of melatonin can help entrain the circadian clock to environmental cycles and have beneficial effects for the treatment of certain forms of insomnia.[90] Prolonged release melatonin has shown good results in treating insomnia in older adults.[91]

Other studies have found that for certain types of sleep disorders, melatonin is not effective. A 2006 review found that although it is safe for short term use (of three months or less), there is "no evidence that melatonin is effective in treating secondary sleep disorders or sleep disorders accompanying sleep restriction, such as jet lag and shiftwork disorder."[92] However, a 2004 review found that melatonin significantly increased total sleep time in people suffering from sleep restriction.[32]

In another study, researchers concluded that while "there is some evidence to suggest that melatonin is effective in treating delayed sleep phase syndrome", ... "There is evidence to suggest that melatonin is not effective in treating most primary sleep disorders with short-term use (4 weeks or less)."[93]

[edit] Dosage

Studies from Massachusetts Institute of Technology have said that melatonin pills sold as supplements contain three to ten times the amount needed to produce the desirable physiologic nocturnal blood melatonin level for a more rapid sleep onset. Dosages are designed to raise melatonin levels for several hours[citation needed] to enhance quality of sleep, but some studies suggest that smaller doses (for example 0.3 mg as opposed to 3 mg) are just as effective.[94]

Large doses of melatonin can even be counterproductive: Lewy et al.[95] provide support to the "idea that too much melatonin may spill over onto the wrong zone of the melatonin phase-response curve" (PRC). In one of their blind subjects, 0.5 mg of melatonin was effective while 20 mg was not.[95][96]

[edit] Availability and safety

Melatonin is available without prescription in most cases in the United States and Canada, while it is available only by prescription or not at all in some other countries. The hormone may be administered orally, as capsules, tablets or liquid, sublingually, or as transdermal patches.

[edit] Dietary supplement

In the USA, because it is sold as a dietary supplement and not as a drug, the Food and Drug Administration (FDA) regulations that apply to medications are not applicable to melatonin.[4] However, new FDA rules required that by June 2010 all production of dietary supplements must comply with "current good manufacturing practices" (cGMP), and be manufactured with "controls that result in a consistent product free of contamination, with accurate labeling."[97] In addition, the industry has been required to report to the FDA "all serious dietary supplement related adverse events" and the FDA has, within the cGMP guidelines, recently begun enforcement of that requirement.

[edit] Pediatrics

While the packaging of melatonin often warns against use in children, at least one long-term study[98] does assess effectiveness and safety in children. No serious safety concerns were noted in any of the 94 cases studied by means of a structured questionnaire for the parents. With a mean follow up time of 3.7 years, long-term medication was effective against sleep onset problems in 88% of the cases.

[edit] Prolonged release for older patients

Melatonin is available as a prolonged-release prescription drug, trade-name Circadin, manufactured by Neurim Pharmaceuticals. The European Medicines Agency (EMA) has approved Circadin 2 mg (prolonged-release melatonin) for patients who are aged 55 or over, as monotherapy for the short-term treatment (up to 13 weeks) of primary insomnia characterized by poor quality of sleep.[99]

[edit] Side effects

Melatonin appears to cause very few side effects in the short term, up to three months, when healthy people take it at low doses. A systematic review[100] in 2006 looked specifically at efficacy and safety in two categories of melatonin usage: first, for sleep disturbances which are secondary to other diagnoses and, second, for sleep disorders such as jet lag and shift work which accompany sleep restriction.

The study concluded that There is evidence that melatonin is safe with short term use.

A similar analysis[93] by the same team a year earlier on the efficacy and safety of exogenous melatonin in the management of primary sleep disorders found that: There is evidence to suggest that melatonin is safe with short-term use (3 months or less).

Some unwanted effects in some people, especially at high doses (~3 mg/day or more) may include: headaches, nausea, next-day grogginess or irritability, hormone fluctuations, vivid dreams or nightmares[101] and reduced blood flow.

While no large, long-term studies which might reveal side effects have been conducted, there do exist case reports about patients who have taken melatonin for years.[102]

Melatonin can cause somnolence (drowsiness), and therefore caution should be shown when driving, operating machinery, etc.

Individuals who experience orthostatic intolerance, a cardiovascular condition that results in reduced blood pressure and blood flow to the brain when a person stands, may experience a worsening of symptoms when taking melatonin supplements, a study at Penn State College of Medicine's Milton S. Hershey Medical Center suggests. Melatonin can exacerbate symptoms by reducing nerve activity in those who experience the condition, the study found.[105]

The use of melatonin derived from animal pineal tissue may carry the risk of contamination or the means of transmitting viral material. The synthetic form of this medication does not carry this risk.[4][106]

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^ Maestroni GJ (2001). "The immunotherapeutic potential of melatonin". Expert Opin Investig Drugs 10 (3): 467–76. doi:10.1517/13543784.10.3.467. PMID 11227046.
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^ Carrillo-Vico A, Lardone PJ, Fernández-Santos JM (2005). "Human lymphocyte-synthesized melatonin is involved in the regulation of the interleukin-2/interleukin-2 receptor system". J. Clin. Endocrinol. Metab. 90 (2): 992–1000. doi:10.1210/jc.2004-1429. PMID 15562014.
^ Cutolo M, Maestroni GJ (2005). "The melatonin-cytokine connection in rheumatoid arthritis". Ann. Rheum. Dis. 64 (8): 1109–11. doi:10.1136/ard.2005.038588. PMID 16014678.
^ a b c Lewis, Alan (1999). Melatonin and the Biological Clock. McGraw-Hill. pp. 23. ISBN 0879837349.
^ Melke J, Botros HG, Chaste P (2008). "Abnormal melatonin synthesis in autism spectrum disorders". Mol Psychiatry 13 (1): 90–8. doi:10.1038/sj.mp.4002016. PMID 17505466.
^ Lewy A, Sack R, Miller L, Hoban T (1987). "Antidepressant and circadian phase-shifting effects of light". Science 235 (4786): 352–4. doi:10.1126/science.3798117. PMID 3798117.
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^ Weichselbaum, Simone (2010-02-07). "New melatonin-based drinks help restless sleepers hit the hay with just a gulp - but pack hormones". Daily News (New York). http://www.nydailynews.com/lifestyle/2010/02/07/2010-02-07_these_drinksll_knock_you_out_dozeinducing_concoctions_include_dose_of_hormones.html.
^ Chronobiotics: Selected Agents of Potential Value in Jet Lag and other Dyschronisms, H. W. Simpson, of Glasgow University, in Chronobiology: Principles and Application to Shifts in Schedules, ed: L.E. Sheving and F. Hagberg, Springer, Berlin, 1979. Retrieved September 23, 2009.
^ Mundey K, Benloucif S, Harsanyi K, Dubocovich ML, Zee PC (October 2005). "Phase-dependent treatment of delayed sleep phase syndrome with melatonin". Sleep 28 (10): 1271–8. PMID 16295212.
^ Lee MY, Kuan YH, Chen HY, Chen TY, Chen ST, Huang CC, Yang IP, Hsu YS, Wu TS, Lee EJ. Intravenous administration of melatonin reduces the intracerebral cellular inflammatory response following transient focal cerebral ischemia in rats. J Pineal Res. 2007 Apr;42(3):297 – 309. PMID 17349029
^ Dominguez-Rodriguez A, Abreu-Gonzalez P, Garcia-Gonzalez MJ, Kaski JC, Reiter RJ, Jimenez-Sosa A. A unicenter, randomized, double-blind, parallel-group, placebo-controlled study of Melatonin as an Adjunct in patients with acute myocardial infarction undergoing primary Angioplasty The Melatonin Adjunct in the acute myocardial infarction treated with Angioplasty (MARIA) trial: Study design and rationale. Contemp Clin Trials. 2006 Oct 17. PMID 17123867.
^ Larson J, Jessen R, Uz T, Arslan A, Kurtuncu M, Imbesi M, Manev H (2006). "Impaired hippocampal long-term potentiation in melatonin MT2 receptor-deficient mice". Neurosci Lett 393 (1): 23–6. doi:10.1016/j.neulet.2005.09.040. PMID 16203090.
^ Pappolla MA, Sos M, Omar RA, Bick RJ, Hickson-Bick DL, Reiter RJ, Efthimiopoulos S, Robakis NK. (1997). "Melatonin prevents death of neuroblastoma cells exposed to the Alzheimer amyloid peptide". J Neurosci 17 (5): 1683–1690. PMID 9030627.
^ Pappolla M, Bozner P, Soto C, Shao H, Robakis NK, Zagorski M, Frangione B, Ghiso J. (1998). "Inhibition of Alzheimer beta-fibrillogenesis by melatonin". J Biol Chem 273 (13): 7185–7188. PMID 9516407.
^ Wang X, Zhang J, Yu X, Han L, Zhou Z, Zhang Y, Wang J (2005). "Prevention of isoproterenol-induced tau hyperphosphorylation by melatonin in the rat". Sheng Li Xue Bao 57 (1): 7–12. PMID 15719129.
^ Volicer L, Harper D, Manning B, Goldstein R, Satlin A (2001). "Sundowning and circadian rhythms in Alzheimer's disease". Am J Psychiatry 158 (5): 704–11. doi:10.1176/appi.ajp.158.5.704. PMID 11329390.
^ Al-Aama, T., Brymer, C., Gutmanis, I., Woolmore-Goodwin, S. M., Esbaugh, J. and Dasgupta, M. , Melatonin decreases delirium in elderly patients: A randomized, placebo-controlled trial. International Journal of Geriatric Psychiatry, n/a. doi: 10.1002/gps.2582
^ Tjon Pian Gi CV, Broeren JP, Starreveld JS, Versteegh FG (2003). "Melatonin for treatment of sleeping disorders in children with attention deficit/hyperactivity disorder: a preliminary open label study". Eur J Pediatr. 162 (7): 554–555. doi:10.1007/s00431-003-1207-x. PMID 12783318.
^ Bellipanni G, DI Marzo F, Blasi F, Di Marzo A (2005). "Effects of melatonin in perimenopausal and menopausal women: our personal experience". Ann N Y Acad Sci 1057 (Dec): 393–402. doi:10.1196/annals.1356.030. PMID 16399909.
^ "Melatonin". About.com: Sleep Disorders: 4.
^ Terzolo M, et al., 1993."Evening administration of melatonin enhances the pulsatile secretion of prolactin but not of LH and TSH in normally cycling women." Clinical Endocrinology, 39(2):185–191.
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^ Gagnier J (2001). "The therapeutic potential of melatonin in migraines and other headache types". Altern Med Rev 6 (4): 383–9. PMID 11578254.
^ http://www.nimh.nih.gov/press/sad-melatonin.cfm
^ Bhattacharjee, Yudhijit (14 September 2007). "Is Internal Timing Key to Mental Health?" (PDF). ScienceMag (AAAS) 317: 1488–90. http://www.ohsu.edu/ohsuedu/academic/som/images/Al-Lewy-Science.pdf. Retrieved 2008-02-18.
^ Lewy AJ, Nurnberger JI, Wehr TA (June 1985). "Supersensitivity to light: possible trait marker for manic-depressive illness". Am J Psychiatry 142 (6): 725–7. PMID 4003592. http://ajp.psychiatryonline.org/cgi/pmidlookup?view=long&pmid=4003592.
^ Whalley LJ, Perini T, Shering A, Bennie J (July 1991). "Melatonin response to bright light in recovered, drug-free, bipolar patients". Psychiatry Res 38 (1): 13–9. doi:10.1016/0165-1781(91)90048-T. PMID 1658841.
^ Mills E, Wu P, Seely D,4; Guyatt G, E; Wu, P; Seely, D; Guyatt, G (2005). "Melatonin in the treatment of cancer: a systematic review of randomized controlled trials and meta-analysis". Journal of pineal research 39 (4): 360. doi:10.1111/j.1600-079X.2005.00258.x. PMID 16207291. http://pt.wkhealth.com/pt/re/jpin/abstract.00005208-200511000-00005.htm.
^ CCNM. Current Research.
^ Navara, KJ; Nelson, RJ (2007). "The dark side of light at night: physiological, epidemiological, and ecological consequences" (Review, PDF: full text). J. Pineal Res. 43 (43): 215–224. doi:10.1111/j.1600-079X.2007.00473.x. PMID 17803517. http://www.psy.ohio-state.edu/nelson/documents/JPinealRes2007.pdf. Retrieved 2008-05-07.
^ Schernhammer E, Rosner B, Willett W, Laden F, Colditz G, Hankinson S (2004). "Epidemiology of urinary melatonin in women and its relation to other hormones and night work". Cancer Epidemiol Biomarkers Prev 13 (62): 936–43. PMID 15184249.
^ a b Koppisetti S, Jenigiri B, Terron MP (October 2008). "Reactive oxygen species and the hypomotility of the gall bladder as targets for the treatment of gallstones with melatonin: a review". Dig. Dis. Sci. 53 (10): 2592–603. doi:10.1007/s10620-007-0195-5. PMID 18338264.
^ Tan D, Manchester LC, Reiter RJ, Qi W, Hanes MA, Farley NJ (October 1999). "High physiological levels of melatonin in the bile of mammals". Life Sci. 65 (23): 2523–9. doi:10.1016/S0024-3205(99)00519-6. PMID 10622237. http://linkinghub.elsevier.com/retrieve/pii/S0024320599005196.
^ Weishaupt, J. H.; et al (November 2006). "Reduced oxidative damage in ALS by high-dose enteral melatonin treatment". J Pineal Res. 41 (4): 313–23. doi:10.1111/j.1600-079X.2006.00377.x. PMID 17014688. http://www.ncbi.nlm.nih.gov/pubmed/17014688. Retrieved 2010-07-03.
^ Wolden-Hanson T, Mitton DR, McCants RL, Yellon SM, Wilkinson CW, Matsumoto AM, Rasmussen Daily melatonin administration to middle-aged male rats suppresses body weight, intraabdominal adiposity, and plasma leptin and insulin independent of food intake and total body fat.Endocrinology.141 (2)487-497, 2000 PMID=10650927.
^ Tan DX, Manchester LC, Fuentes-Broto L, Paredes SD, Reiter RJ. Significance and application of melatonin in the regulation of brown adipose tissue metabolism: relation to human obesity.Obes Rev. 2010 Jun 16. [Epub ahead of print | PMID 20557470
^ From Ross' Histology and Wheater's Functional Histology.Template:Full citations needed
^ Areechun Sotthibundhu1, Pansiri Phansuwan-Pujito, Piyarat Govitrapong (2010). “Melatonin increases proliferation of cultured neural stem cells obtained from adult mouse subventricular zone”. Journal of Pineal Research 49 (3): 291-300. DOI: 10.1111/j.1600-079X.2010.00794.x
^ Basu P.P., Pacana T., Shah N., Hampole H., Krishnaswamy N., Rayapudi K. "Role of melatonin in colonic motility in irritable bowel syndrome - Constipation MIMI-C-a double blinded randomized placebocontrol clinical trial" Neurogastroenterology and Motility 2010 22 SUPPL. 1 (67)
^ Turek FW, Gillette MU (November 2004). "Melatonin, sleep, and circadian rhythms: rationale for development of specific melatonin agonists". Sleep Med. 5 (6): 523–32. doi:10.1016/j.sleep.2004.07.009. PMID 15511698.
^ Wade AG, Ford I, Crawford G (October 2007). "Efficacy of prolonged release melatonin in insomnia patients aged 55–80 years: quality of sleep and next-day alertness outcomes". Curr Med Res Opin 23 (10): 2597–605. doi:10.1185/030079907X233098. PMID 17875243.
^ Buscemi, Nina; Vandermeer, B; Hooton, N; Pandya, R; Tjosvold, L; Hartling, L; Vohra, S; Klassen, TP et al. (2006-02-18). "Efficacy and safety of exogenous melatonin for secondary sleep disorders and sleep disorders accompanying sleep restriction: meta-analysis". BMJ 332 (7538): 385–393. doi:10.1136/bmj.38731.532766.F6. PMID 16473858. PMC 1370968. http://www.bmj.com/cgi/content/full/332/7538/385. Retrieved 2008-05-17.
^ a b Buscemi N, Vandermeer B, Hooton N, et al. (December 2005). "The efficacy and safety of exogenous melatonin for primary sleep disorders. A meta-analysis". Journal of General Internal Medicine 20 (12): 1151–8. doi:10.1111/j.1525-1497.2005.0243.x. PMID 16423108.
^ Zhdanova I, Wurtman R, Regan M, Taylor J, Shi J, Leclair O (2001). "Melatonin treatment for age-related insomnia". J Clin Endocrinol Metab 86 (10): 4727–30. doi:10.1210/jc.86.10.4727. PMID 11600532.
^ a b Lewy AJ, Emens JS, Sack RL, Hasler BP, Bernert RA (2002). "Low, but not high, doses of melatonin entrained a free-running blind person with a long circadian period". Chronobiol Int. 19 (3): 649–58. doi:10.1081/CBI-120004546. PMID 12069043.
^ Sack, Robert L.; Richard W. Brandes, Adam R. Kendall, Alfred J. Lewy (October 2000). "Entrainment of Free-Running Circadian Rhythms by Melatonin in Blind People" (Full text). New England Journal of Medicine (343): 1070–77. http://www.nejm.org/doi/full/10.1056/NEJM200010123431503#t=article. Retrieved 2010-12-01.
^ U.S. Food and Drug Administration (2007-06-22). "FDA Issues Dietary Supplements Final Rule". Press release. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2007/ucm108938.htm. Retrieved 2009-08-04.
^ Hoebert M, van der Heijden KB, van Geijlswijk IM, Smits MG (August 2009). "Long-term follow-up of melatonin treatment in children with ADHD and chronic sleep onset insomnia". Journal of Pineal Research 47 (1): 1–7. doi:10.1111/j.1600-079X.2009.00681.x. PMID 19486273.
^ Medical News Today Circadin (Prolonged-Release Melatonin) For Primary Insomnia Recommended For Approval In The EU (27 Apr 2007)
^ Buscemi, Nina; Vandermeer, B; Hooton, N; Pandya, R; Tjosvold, L; Hartling, L; Vohra, S; Klassen, TP et al. (2006-02-18). "Efficacy and safety of exogenous melatonin for secondary sleep disorders and sleep disorders accompanying sleep restriction: meta-analysis". BMJ 332 (7538): 385–393. doi:10.1136/bmj.38731.532766.F6. PMID 16473858. PMC 1370968. http://www.bmj.com/cgi/content/full/332/7538/385. Retrieved 2008-05-17.
^ "melatonin cautions". www.melatonin.com. http://www.melatonin.com/melatonin-cautions.php.
^ Sack, Robert L.; Brandes, RW; Kendall, AR; Lewy, AJ (12 October 2000). "Entrainment of Free-Running Circadian Rhythms by Melatonin in Blind People". The NEW ENGLAND JOURNAL of MEDICINE 343 (15): 1070–1077. doi:10.1056/NEJM200010123431503. PMID 11027741. http://content.nejm.org/cgi/content/abstract/343/15/1070. Retrieved 2008-04-13.
^ Morera A, Henry M, de La Varga M (2001). "Safety in melatonin use". Actas Esp Psiquiatr 29 (5): 334–7. PMID 11602091.
^ Terry PD, Villinger F, Bubenik GA, Sitaraman SV (January 2009). "Melatonin and ulcerative colitis: evidence, biological mechanisms, and future research". Inflammatory Bowel Diseases 15 (1): 134–40. doi:10.1002/ibd.20527. PMID 18626968.
^ Penn State College of Medicine, Milton S. Hershey Medical Center (September 2003). "Study Shows Melatonin Supplements May Make Standing A Hazard For The Cardiovascular-Challenged" (DOC). Press release. http://www.hmc.psu.edu/news/pr/2003/sept/Ray_melatonin.doc. Retrieved 2006-07-21. (MS Word Format)
^ "Melatonin Information from Drugs.com". http://www.drugs.com/melatonin.html.

[edit] External links

[show]v · d · e Melatonergics

Receptor
ligands

Agonists	Agomelatine • LY-156,735 • Melatonin • NAS (Normelatonin) • Ramelteon • Tasimelteon

Antagonists	Afobazole • Luzindole

Enzyme
inhibitors

Anabolism

AANAT inhibitors

ASMT inhibitors

Catabolism

Others

Precursors	L-Tryptophan → 5-HTP → Serotonin → NAS (Normelatonin)

Cofactors	Ferrous Iron (Fe2+) • Magnesium (Mg2+) • S-Adenosyl-L-methionine • Tetrahydrobiopterin • Vitamin B3 (Niacin, nicotinamide → NADPH) • Vitamin B6 (Pyridoxine, Pyridoxamine, Pyridoxal → Pyridoxal phosphate) • Vitamin B9 (Folic acid → Tetrahydrofolic acid) • Vitamin C (Ascorbic acid) • Zinc (Zn2+)

[show]v · d · e Neurotransmitters

Amino acids

Alanine · Aspartate · Cycloserine · DMG · GABA · Glutamate · Glycine · Hypotaurine · Kynurenic acid (Transtorine) · NAAG (Spaglumic acid) · NMG (Sarcosine) · Serine · Taurine · TMG (Betaine)

Endocannabinoids

2-AG · 2-AGE (Noladin ether) · AEA (Anandamide) · NADA · OAE (Virodhamine) · Oleamide · PEA (Palmitoylethanolamide) · RVD-Hpα · Hp (Hemopressin)

Gasotransmitters

Carbon monoxide · Hydrogen sulfide · Nitric oxide · Nitrous oxide

Monoamines

Dopamine · Epinephrine (Adrenaline) · Melatonin · NAS (Normelatonin) · Norepinephrine (Noradrenaline) · Serotonin (5-HT)

Purines

Adenosine · ADP · AMP · ATP

Trace amines

3-ITA · 5-MeO-DMT · Bufotenin · DMT · NMT · Octopamine · Phenethylamine · Synephrine · Thyronamine · Tryptamine · Tyramine

Others

1,4-BD · Acetylcholine · GBL · GHB · Histamine

See also Template:Neuropeptides

M: PNS

anat(h, r, t, c, b, l, s)/phys/devp/prot/nttr/nttm/ntrp

noco/auto/cong/tumr, sysi/epon, injr

proc, drug(N1B)

[show]v · d · e Antioxidants

Acetyl-L-Carnitine (ALCAR) • Alpha-Lipoic Acid (ALA) • Ascorbic Acid (Vitamin C) • Carotenoids (Vitamin A) • Curcumin • Edaravone • Flavonoids (Quercetin, Kaempferol, Catechin, EGCG, etc) • Gallic Acid • Glutathione • Hydroxytyrosol • L-Carnitine • Ladostigil • Melatonin • N-Acetylcysteine (NAC) • N-Acetylserotonin (NAS) • Oleocanthal • Oleuropein • Rasagiline • Resveratrol • Selegiline • Selenium • Tocopherols (Vitamin E) • Tocotrienols (Vitamin E) • Tyrosol • Ubiquinone (Coenzyme Q) • Uric Acid

[show]v · d · e Dietary supplements

Types	Amino acids • Bodybuilding supplement • Energy drink • Energy bar • Fatty acids • Herbal Supplements • Minerals • Prebiotics • Probiotics (Lactobacillus, Bifidobacterium) • Vitamins

Vitamins and "minerals" (chemical elements)	Retinol (Vitamin A) • B vitamins: Thiamine (B1) • Riboflavin (B2) • Niacin (B3) • Pantothenic acid (B5) • Pyridoxine (B6) • Biotin (B7) • Folic acid (B9) • Cyanocobalamin (B12) • Ascorbic acid (Vitamin C) • Ergocalciferol and Cholecalciferol (Vitamin D) • Tocopherol (Vitamin E) • Naphthoquinone (Vitamin K) • Calcium • Choline • Chlorine • Chromium • Cobalt • Copper • Fluorine • Iodine • Iron • Magnesium • Manganese • Molybdenum • Phosphorus • Potassium • Selenium • Sodium • Sulfur • Zinc

Other common ingredients	AAKG • Carnitine • Chondroitin sulfate • Cod liver oil • Copper gluconate • Creatine/Creatine supplements • Dietary fiber • Echinacea • Elemental calcium • Ephedra • Fish oil • Folic acid • Ginseng • Glucosamine • Glutamine • Grape seed extract • Iron supplements • Japanese Honeysuckle • Krill oil • Lingzhi • Linseed oil • Lipoic acid • Milk thistle • Melatonin • Red yeast rice • Royal jelly • Saw palmetto • Spirulina • St John's wort • Taurine • Wheatgrass • Wolfberry • Yohimbine • Zinc gluconate

Related articles	Codex Alimentarius • Enzyte • Hadacol • Nutraceutical • Multivitamin • Nutrition

[show]v · d · e Endocrine system: hormones (Peptide hormones · Steroid hormones)

Endocrine
glands

Hypothalamic-
pituitary

Hypothalamus	GnRH · TRH · Dopamine · CRH · GHRH/Somatostatin · Melanin concentrating hormone

Posterior pituitary	Vasopressin · Oxytocin

Anterior pituitary	α (FSH FSHB, LH LHB, TSH TSHB, CGA) · Prolactin · POMC (CLIP, ACTH, MSH, Endorphins, Lipotropin) · GH

Adrenal axis

Adrenal cortex: aldosterone · cortisol · DHEA
Adrenal medulla: epinephrine · norepinephrine

Thyroid axis

Thyroid: thyroid hormone (T3 and T4) · calcitonin
Parathyroid: PTH

Gonadal axis

Testis: testosterone · AMH · inhibin

Ovary: estradiol · progesterone · activin and inhibin · relaxin (pregnancy)

Placenta: hCG · HPL · estrogen · progesterone

Other end.
glands

Pancreas: glucagon · insulin · somatostatin

Pineal gland: melatonin

Non-end.
glands

Thymus: Thymosin (Thymosin α1, Thymosin beta) · Thymopoietin · Thymulin

digestive system: Stomach: gastrin · ghrelin · Duodenum: CCK · GIP · secretin · motilin · VIP · Ileum: enteroglucagon · Liver/other: Insulin-like growth factor (IGF-1, IGF-2)

Adipose tissue: leptin · adiponectin · resistin

Skeleton: Osteocalcin

Kidney: JGA (renin) · peritubular cells (EPO) · calcitriol · prostaglandin

Heart: Natriuretic peptide (ANP, BNP)

M: END

anat/phys/devp/horm/cell

noco(d)/cong/tumr, sysi/epon

proc, drug (A10/H1/H2/H3/H5)

[show]v · d · e Hypnotics/Sedatives (N05C)

GABAA receptor

Barbiturates

Ultrashort-acting	Methohexital • Thiamylal • Thiopental

Short/intermediate- acting	Allobarbital • Amobarbital • Butabarbital • Butobarbital • Pentobarbital • Secobarbital • Talbutal

Long-acting	Barbital • Mephobarbital • Phenobarbital

Ungrouped	Cyclobarbital • Ethallobarbital • Heptabarbital • Hexobarbital • Proxibarbal • Reposal • Vinylbital • Vinbarbital

Benzodiazepines

Short-acting	Brotizolam • Cinolazepam • Doxefazepam • Loprazolam • Midazolam • Triazolam

Intermediate-acting	Estazolam • Flunitrazepam • Lormetazepam • Nimetazepam • Temazepam

Long-acting	Flurazepam • Flutoprazepam • Nitrazepam • Quazepam

Dialkylphenols

Fospropofol • Propofol • Thymol

Nonbenzo-
diazepines

CL-218,872 • Eszopiclone • Indiplon • Lirequinil • Necopidem • Pazinaclone • ROD-188 • Saripidem • Suproclone • Suriclone • SX-3228 • U-89843A • U-90042 • Zaleplon • Zolpidem • Zopiclone

Piperidinediones

Glutethimide • Methyprylon • Pyrithyldione • Piperidione

Quinazolinones

Afloqualone • Cloroqualone • Diproqualone • Etaqualone • Mebroqualone • Mecloqualone • Methaqualone • Methylmethaqualone • Nitromethaqualone

Neuroactive
steroids

Acebrochol • Allopregnanolone • Alphadolone • Alphaxolone • Eltanolone • Ganaxolone • Hydroxydione • Minaxolone • Org 20599 • Org 21465 • Tetrahydrodeoxycorticosterone

Alpha-2 adrenergic
receptor

Alpha-adrenergic agonists

4-NEMD • Clonidine • Dexmedetomidine • Lofexidine • Medetomidine • Romifidine • Tizanidine • Xylazine

Melatonin receptor

Melatonin

Agomelatine • Melatonin • Ramelteon • Tasimelteon

Histamine receptor &
Acetylcholine receptor

Antihistamines &
Anticholinergics

Amitriptyline • Dimenhydrinate • Doxylamine • Hydroxyzine • Diphenhydramine • Bromodiphenhydramine • Carbinoxamine • Doxepin • Esmirtazapine • Orphenadrine • Mianserin • Mirtazapine • Phenyltoloxamine • Propiomazine • Pyrilamine • Scopolamine

5-HT2A &
α1-adrenergic

Selective 5-HT2A & α1-adrenergic antagonists

Etoperidone • Nefazodone • Niaprazine • Trazodone

GABAB receptor /
GHB receptor

GHB Type

1,4-Butanediol • Aceburic acid • GABOB • gamma-Hydroxybutyric acid • GBL • gamma-Valerolactone

Orexin receptors

Orexin antagonists

Almorexant • SB-334,867 • SB-408,124 • SB-649,868 • TCS-OX2-29

Other receptors/
ungrouped

Aldehydes

Acetylglycinamide chloral hydrate • Chloral hydrate • Chloralodol • Dichloralphenazone • Paraldehyde • Petrichloral

Alkynes

Centalun • Ethchlorvynol • Ethinamate • Hexapropymate • Methylpentynol

Carbamates

Meprobamate • Carisoprodol • Tybamate • Methocarbamol • Procymate

Other

2-Methyl-2-butanol • Acecarbromal • Acetophenone • Apronal • Bromides • Bromisoval • Carbromal • Chloralose • Clomethiazole • Embutramide • Etomidate • Evoxine • Fenadiazole • Gaboxadol • Loreclezole • Mephenoxalone • Sulfonmethane • Trichloroethanol • Triclofos • Valerian • Valnoctamide

#WHO-EM. ‡Withdrawn from market. Clinical trials: †Phase III. §Never to phase III

M: PSO/PSI

mepr

dsrd (o, p, m, p, a, d, s), sysi/epon, spvo

proc, drug(N5A/5B/5C/6A/6B/6D)

[show]v · d · e Antidepressants (N06A)

[show] Specific reuptake inhibitors (RIs), enhancers (REs), and releasing agents (RAs)

Selective serotonin reuptake inhibitors (SSRIs)	Alaproclate • Citalopram • Escitalopram • Femoxetine • Fluoxetine • Fluvoxamine • Indalpine • Ifoxetine • Litoxetine • Lubazodone • Panuramine • Paroxetine • Pirandamine • Seproxetine • Sertraline • Vilazodone • Zimelidine

Serotonin-norepinephrine reuptake inhibitors (SNRIs)	Bicifadine • Clovoxamine • Desvenlafaxine • Duloxetine • Levomilnacipran • Eclanamine • Milnacipran • Sibutramine • Venlafaxine

Serotonin-norepinephrine-dopamine reuptake inhibitors (SNDRIs)	Brasofensine • BTS-74,398 • Cocaine • Diclofensine • DOV-21,947 • DOV-102,677 • DOV-216,303 • EXP-561 • Fezolamine • JNJ-7,925,476 • NS-2359 • PRC200-SS • Pridefrine • SEP-225,289 • SEP-227,162 • Tesofensine

Norepinephrine reuptake inhibitors (NRIs)	Amedalin • Atomoxetine/Tomoxetine • Binedaline • Ciclazindol • Daledalin • Esreboxetine • Lortalamine • Mazindol • Nisoxetine • Reboxetine • Talopram • Talsupram • Tandamine • Viloxazine

Dopamine reuptake inhibitors (DRIs)	Medifoxamine • Vanoxerine

Norepinephrine-dopamine reuptake inhibitors (NDRIs)	Amineptine • Bupropion/Amfebutamone • Cilobamine • Manifaxine • Methylphenidate • Nomifensine • Radafaxine • Tametraline

Norepinephrine-dopamine releasing agents (NDRAs)	Amphetamine • Befuraline • Lisdexamfetamine • Methamphetamine • Phenethylamine • Piberaline • Tranylcypromine

Serotonin-norepinephrine-dopamine releasing agents (SNDRAs)	4-Methyl-αMT • αET/Etryptamine • αMT/Metryptamine

Selective serotonin reuptake enhancers (SSREs)	Tianeptine

Others	Indeloxazine • Tramadol • Viqualine

[show] Receptor antagonists and/or reuptake inhibitors

Serotonin antagonists and reuptake inhibitors (SARIs)	Etoperidone • Nefazodone • Trazodone

Noradrenergic and specific serotonergic antidepressants (NaSSAs)	Aptazapine • Esmirtazapine • Mianserin • Mirtazapine • Setiptiline/Teciptiline

Norepinephrine-dopamine disinhibitors (NDDIs)	Agomelatine

Serotonin modulators and stimulators (SMSs)	Lu AA21004

[show] Tricyclic and tetracyclic antidepressants (TCAs/TeCAs)

Tricyclics: Amezepine • Amineptine • Amitriptyline • Amitriptylinoxide • Azepindole • Butriptyline • Cianopramine • Clomipramine • Cotriptyline • Cyanodothiepin • Demexiptiline • Depramine/Balipramine • Desipramine • Dibenzepine • Dimetacrine • Dosulepin/Dothiepin • Doxepin • Enprazepine • Fluotracen • Hepzidine • Homopipramol • Imipramine • Imipraminoxide • Intriptyline • Iprindole • Ketipramine • Litracen • Lofepramine • Losindole • Mariptiline • Melitracen • Metapramine • Mezepine • Naranol • Nitroxazepine • Nortriptyline • Noxiptiline • Octriptyline • Opipramol • Pipofezine • Propizepine • Protriptyline • Quinupramine • Tampramine • Tianeptine • Tienopramine • Trimipramine; Tetracyclics: 7-OH-Amoxapine • Amoxapine • Aptazapine • Azipramine • Ciclazindol • Ciclopramine • Esmirtazapine • Loxapine • Maprotiline • Mazindol • Mianserin • Mirtazapine • Oxaprotiline • Setiptiline/Teciptiline

[show] Monoamine oxidase inhibitors (MAOIs)

Nonselective: Irreversible: Benmoxin • Echinopsidine • Iproclozide • Iproniazid • Isocarboxazid • Mebanazine • Metfendrazine • Nialamide • Octamoxin • Phenelzine • Pheniprazine • Phenoxypropazine • Pivalylbenzhydrazine • Safrazine • Tranylcypromine; Reversible: Caroxazone • Paraxazone; MAOA-Selective: Irreversible: Clorgyline; Reversible: Amiflamine • Bazinaprine • Befloxatone • Befol • Brofaromine • Cimoxatone • Esuperone • Harmala Alkaloids (Harmine, Harmaline, Tetrahydroharmine, Harman, Norharman, etc) • Methylene Blue • Metralindole • Minaprine • Moclobemide • Pirlindole • Sercloremine • Tetrindole • Toloxatone • Tyrima; MAOB-Selective: Irreversible: Ladostigil • Mofegiline • Pargyline • Rasagiline • Selegiline; Reversible: Lazabemide • Milacemide

[show] Azapirones and other 5-HT1A receptor agonists

Alnespirone • Aripiprazole • Befiradol • Buspirone • Eptapirone • Flesinoxan • Flibanserin • Gepirone • Ipsapirone • Oxaflozane • Tandospirone • Vilazodone • Zalospirone

[show] Dietary supplements (vitamins, minerals, amino acids, etc)

Ascorbic acid (Vitamin C) • Fish oil • Folic acid (Vitamin B9) • L-5-HTP (Oxitriptan) • L-DOPA (Levodopa) • L-Methionine • L-Phenylalanine • L-Tryptophan • L-Tyrosine • Lithium • Magnesium • Melatonin • Niacin/Niacinamide (Vitamin B3) • Omega-3 fatty acids • Pyridoxine (Vitamin B6) • Rubidium • SAMe • Zinc

[show] Research compounds and miscellaneous agents

5-HT4R agonists	RS-67,333 • SL65.0155

5-HT7R antagonists	Amisulpride

α2δ-VDCC blockers	Gabapentin • Pregabalin

β3-Adrenoceptor agonists	Amibegron • Solabegron

σ1R agonists	Afobazole • Dextromethorphan • Fluvoxamine • Igmesine • Opipramol • PRE-084

CB1R agonists	Nabilone • Tetrahydrocannabinol/Dronabinol

COMT inhibitors	Entacapone • Tolcapone

CRF1R antagonists	Antalarmin • CP-154,526 • Pexacerfont • Pivagabine

D2/D3 AR antagonists	Amisulpride • Sulpiride

D2/D3/D4 R agonists	Piribedil • Pramipexole • Ropinirole • Rotigotine • Roxindole

DOR agonists	BU-48 • Buprenorphine • BW373U86 • DPI-287 • Heroin • Kratom • SNC-80

Enkephalinase inhibitors	D-Phenylalanine • RB-101

FAAH inhibitors	Acetaminophen/Paracetamol • AM-404 • URB-597

KOR antagonists	5-GNTI • Buprenorphine • JDTic • Norbinaltorphimine

MOR agonists	Buprenorphine • Codeine • Dextropropoxyphene • Dihydrocodeine • Fentanyl • Heroin • Hydrocodone • Hydromorphone • Kratom • Methadone • Morphine • Opium • Oxycodone • Oxymorphone • Pethidine/Meperidine • Tapentadol • Tramadol

MT1/MT2R agonists	Agomelatine • Melatonin • Ramelteon • Tasimelteon

NK1R antagonists	Aprepitant • Casopitant • Fosaprepitant • L-733,060 • Maropitant • Vestipitant

NMDAR antagonists	Dextromethorphan • Ketamine • Magnesium • Memantine • Zinc

PDE4 inhibitors	Mesembrine (Kanna) • Rolipram

TRPC6 activators	Adhyperforin (St. John's Wort) • Hyperforin (St. John's Wort)

M: PSO/PSI

mepr

dsrd (o, p, m, p, a, d, s), sysi/epon, spvo

proc, drug(N5A/5B/5C/6A/6B/6D)

[show]v · d · eDrugs from TiHKAL

AL-LAD • DBT • DET • DiPT • 5-MeO-α-MT • DMT • 2,α-DMT • α,N-DMT • DPT • EiPT • α-ET • ETH-LAD • Harmaline • Harmine • 4-HO-DBT • 4-HO-DET • 4-HO-DiPT • 4-HO-DMT • 5-HO-DMT • 4-HO-DPT • 4-HO-MET • 4-HO-MiPT • 4-HO-MPT • 4-HO-pyr-T • Ibogaine • LSD • MBT • 4,5-MDO-DiPT • 5,6-MDO-DiPT • 4,5-MDO-DMT • 5,6-MDO-DMT • 5,6-MDO-MiPT • 2-Me-DET • 2-Me-DMT • Melatonin • 5-MeO-DET • 5-MeO-DiPT • 5-MeO-DMT • 4-MeO-MiPT • 5-MeO-MiPT • 5,6-MeO-MiPT • 5-MeO-NMT • 5-MeO-pyr-T • 6-MeO-THH • 5-MeO-TMT • 5-MeS-DMT • MiPT • α-MT • NET • NMT • PRO-LAD • pyr-T • Tryptamine • Tetrahydroharmine • α,N,O-TMS

[show]v · d · e Tryptamines

2-Methyl-5-HT • 4-Acetoxy-DET • 4-Acetoxy-DIPT • 4-Acetoxy-DMT • 4-HO-αMT • 4-HO-DIPT • 4-HO-MET • 4-MeO-DMT • 4-Methyl-αET • 4-Methyl-αMT • 5-Benzyloxytryptamine • 5-Bromo-DMT • 5-Carboxamidotryptamine • 5-Fluoro-αMT • 5-HO-αMT • 5-HTP • 5-Fluoro-DMT • 5-Methyl-DMT • 5-Methoxytryptamine • 5-MeO-7,N,N-TMT • 5-MeO-αET • 5-MeO-αMT • 5-MeO-DALT • 5-MeO-DET • 5-MeO-DIPT • 5-MeO-DMT • 5-MeO-DPT • 5-MeO-MIPT • 5,7-Dihydroxytryptamine • 7-Methyl-αET • 7-Methyl-DMT • αET • αMT • Aeruginascin • AL-37350A • BW-723C86 • Baeocystin • Bufotenidine • Bufotenin • DALT • Desformylflustrabromine • DET • DiPT • DMT • DPT • Ethocybin • EiPT • EMDT • Ethocin • FGIN-127 • FGIN-143 • Ibogaine • Iprocin • MET • MiPT • Miprocin • Melatonin • MS-245 • NAS • NMT • Norbaeocystin • Normelatonin • Oxypertine • PiPT • Psilocin • Psilocybin • Rizatriptan • Serotonin • Sumatriptan • Tryptamine • Tryptophan • Yohimbine • Yuremamine • Zolmitriptan

Retrieved from "http://en.wikipedia.org/wiki/Melatonin"

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Melatonin

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