Melatonin Chemical formula

💊 Chemical information

N-Acetyl-5-methoxytryptamine; Melatoniini; Melatonina; Melatoninum. N-[2-(5-Methoxyindol-3-yl)ethyl]acetamide.
Chemical formula: C13H16N2O2 = 232.3.
CAS — 73-31-4.
ATC — N05CH01.
ATC Vet — QN05CH01.

💊 Profile

Melatonin is a hormone produced in the pineal gland from the amino acid tryptophan. Results mainly from animal studies indicate that melatonin increases the concentration of aminobutyric acid and serotonin in the midbrain and hypothalamus and enhances the activity of pyridoxal-kinase, an enzyme involved in the synthesis of aminobutyric acid, dopamine, and serotonin. Melatonin is involved in the inhibition of gonadal development and in the control of oestrus. It is also involved in protective changes in skin coloration. There appears to be a diurnal rhythm of melatonin secretion; it is secreted during hours of darkness and may affect sleep pattern. Because of its possible role in influencing circadian rhythm, melatonin has been tried in the alleviation of jet lag and other disorders resulting from delay of sleep. Doses of 2 mg given orally before bedtime are used in the shortterm management of insomnia in patients aged 55 or over. Melatonin has also been studied in various depressive disorders including seasonal affective disorder, and in large doses for its contraceptive activity. A number of melatonin analogues are being developed.

Adverse effects.

An increase in seizure activity was noted in 4 of 6 children with severe neurological deficits during treatment with melatonin for sleep disorders.1 Seizure activity returned to baseline values when melatonin was stopped and recurred on rechallenge.
1. Sheldon SH. Pro-convulsant effects of oral melatonin in neurologically disabled children. Lancet 1998; 351: 1254.


Melatonin has been tried in a number of disorders1 including, in large doses, as an adjunct to conventional chemotherapy for malignant neoplasms2,3 and, with norethisterone, as a contraceptive.4 It is possible that contraceptive use of melatonin may be associated with a reduced risk of breast cancer.5 For mention of response to melatonin in 2 patients with sarcoidosis. Preliminary studies have also suggested that melatonin may be beneficial in hyperlipidaemias,6 cluster headaches,7 tinnitus,8alopecia in women,9 and irritable bowel syndrome associated with sleep disturbances.10 Repeated bedtime doses may also play a part in reducing nocturnal blood pressure in patients with essential hypertension.11 Claims for its value as an anti-ageing treatment and for use in conditions such as Alzheimer’s disease and AIDS are unfounded.2,12 The effects of long-term use of melatonin have yet to be assessed.
1. Wetterberg L. Melatonin and clinical application. Reprod Nutr Dev 1999; 39: 367–82
2. Pepping J. Melatonin. Am J Health-Syst Pharm 1999; 56: 2520–7
3. Lissoni P, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999; 35: 1688–92
4. Short RV. Melatonin. BMJ 1993; 307: 952–3
5. Cohen M, et al. Hypotheses: melatonin/steroid combination contraceptives will prevent breast cancer. Breast Cancer Res Treat 1995; 33: 257–64
6. Pittalis S, et al. Effect of a chronic therapy with the pineal hormone melatonin on cholesterol levels in idiopathic hypercholesterolemic patients. Recenti Prog Med 1997; 88: 401–2
7. Leone M, et al. Melatonin versus placebo in the prophylaxis of cluster headache; a double-blind pilot study with parallel groups. Cephalalgia 1996; 16: 494–6
8. Rosenberg SI, et al. Effect of melatonin on tinnitus. Laryngoscope 1998; 108: 305–10
9. Fischer TW, et al. Melatonin increases anagen hair rate in women with androgenetic alopecia or diffuse alopecia: results of a pilot randomized controlled trial. Br J Dermatol 2004; 150: 341–5
10. Song GH, et al. Melatonin improves abdominal pain in irritable bowel syndrome patients who have sleep disturbances: a randomised, double blind, placebo controlled study. Gut 2005; 54: 1402–7
11. Scheer FAJL, et al. Daily nighttime melatonin reduces blood pressure in male patients with essential hypertension. Hypertension 2004; 43: 192–7
12. Brzezinski A. Melatonin in humans. N Engl J Med 1997; 336: 186–95.
INSOMNIA. Although melatonin is considered1-6 to be potentially useful in the management of various forms of insomnia, especially those associated with circadian rhythm disturbances, there is little evidence of efficacy from large studies and its long-term safety remains to be established. A meta-analysis7 of randomised controlled studies concluded that melatonin does not have a significant effect on sleep onset latency in secondary sleep disorders or those accompanying sleep restriction such as jet lag and shift work. In healthy subjects melatonin has been reported8,9 to reduce the time to onset of sleep and to increase the time spent asleep. Whether this is due to adjustment of the ‘body clock’ or any hypnotic action of melatonin is unclear. Measurement of nocturnal urinary excretion of the major metabolite, 6-sulfatoxymelatonin, demonstrated that low nocturnal melatonin production is associated with insomnia in patients over 55 years of age, and might identify those more likely to respond to treatment with melatonin.10 Improved quality of sleep has been reported in elderly patients treated with melatonin for insomnia,11 and it might be of use in delayed sleep phase syndrome12 and insomnia in shift workers and totally blind people, although some13,14 have found no beneficial effects of melatonin in night shift workers or emergency medicine employees. There has also been a report15 of a patient with somnolence associated with melatonin deficiency after pinealectomy who responded to treatment with melatonin. A preliminary report16has suggested that use of melatonin may enable benzodiazepine therapy for insomnia to be stopped without impairing the quality of sleep. However, melatonin might adversely affect sleep patterns in some circumstances.17
1. Haimov I, Lavie P. Potential of melatonin replacement therapy in older patients with sleep disorders. Drugs Aging 1995; 7: 75–8
2. Brown GM. Melatonin in psychiatric and sleep disorders: therapeutic implications. CNS Drugs 1995; 3: 209–26
3. Anonymous. Melatonin. Med Lett Drugs Ther 1995; 37: 111–12
4. Arendt J. Melatonin. BMJ 1996; 312: 1242–3
5. Lamberg L. Melatonin potentially useful but safety, efficacy remain uncertain. JAMA 1996; 276: 1011–14
6. Skene DJ, et al. Use of melatonin in the treatment of phase shift and sleep disorders. Adv Exp Med Biol 1999; 467: 79–84
7. Buscemi N, et al. Efficacy and safety of exogenous melatonin for secondary sleep disorders and sleep disorders accompanying sleep restriction: meta-analysis. Abridged version: BMJ 2006; 332: 385–8. Full version: 7538/385 (accessed 25/07/08
8. Zhdanova IV, et al. Sleep-inducing effects of low doses of melatonin ingested in the evening. Clin Pharmacol Ther 1995; 57: 552–8
9. Attenburrow MEJ, et al. Low dose melatonin improves sleep in middle-aged subjects. Psychopharmacology (Berl) 1996; 126: 179–81
10. Leger D, et al. Nocturnal 6-sulfatoxymelatonin excretion in insomnia and its relation to the response to melatonin replacement therapy. Am J Med 2004; 116: 91–5
11. Garfinkel D, et al. Improvement of sleep quality in elderly people by controlled-release melatonin. Lancet 1995; 346: 541–4
12. Nagtegaal JE, et al. Effects of melatonin on the quality of life in patients with delayed sleep phase syndrome. J Psychosom Res 2000; 48: 45–50
13. Wright SW, et al. Randomized clinical trial of melatonin after night-shift work: efficacy and neuropsychologic effects. Ann Emerg Med 1998; 32: 334–40
14. Jockovich M, et al. Effect of exogenous melatonin on mood and sleep efficiency in emergency medicine residents working night shifts. Acad Emerg Med 2000; 7: 955–8
15. Lehmann ED, et al. Somnolence associated with melatonin deficiency after pinealectomy. Lancet 1996; 347: 323
16. Garfinkel D, et al. Facilitation of benzodiazepine discontinuation by melatonin: a new clinical approach. Arch Intern Med 1999; 159: 2456–60
17. Middleton BA, et al. Melatonin and fragmented sleep patterns. Lancet 1996; 348: 551–2.
JET LAG. Melatonin has been reported to alleviate jet lag following long flights.1-4 The most appropriate dosing schedule has yet to be determined but will depend on both the direction of travel and the distance travelled. A systematic review5 concluded that melatonin was effective in preventing or reducing jet lag in those travelling across 5 or more time zones, particularly in an easterly direction, and especially if jet lag had been experienced previously; travellers crossing 2 to 4 time zones might also derive benefit. However, a meta-analysis6 of randomised controlled studies concluded that melatonin does not have a significant effect on sleep onset latency accompanying jet lag.
1. Waterhouse J, et al. Jet-lag. Lancet 1997; 350: 1611–16
2. Arendt J. Jet-lag. Lancet 1998; 351: 293–4
3. Arendt J. Jet-lag and shift work: (2) therapeutic use of melatonin. J R Soc Med 1999; 92: 402–5
4. Waterhouse J, et al. Jet lag: trends and coping strategies. Lancet 2007; 369: 1117–29
5. Herxheimer A, Petrie KJ. Melatonin for the prevention and treatment of jet lag. Available in The Cochrane Database of Systematic Reviews; Issu
2. Chichester: John Wiley; 2002 (accessed 28/04/05)
6. Buscemi N, et al. Efficacy and safety of exogenous melatonin for secondary sleep disorders and sleep disorders accompanying sleep restriction: meta-analysis. Abridged version: BMJ 2006; 332: 385–8. Full version: 7538/385 (accessed 25/07/08)

💊 Preparations

Proprietary Preparations

Arg.: Armonil Noche; Buenas Noches; Melatol; Nochix†; Repentil†; Chile: Novel†; Hong Kong: Melapure†; Hung.: Bio-Melatonin; India: Meloset; Mex.: Benedorm; Cronocaps; Revenox†; Port.: Circadin; Rus.: Melaxen (Мелаксен); UK: Circadin; USA: Transzone. Multi-ingredient: Arg.: Plenovit Melatonina; India: Eternex; Stresnil; USA: Bevitamel; Melagesic PM.
Published May 08, 2019.