New approaches in the management of insomnia: weighing the advantages of prolonged-release melatonin and synthetic melatoninergic agonists
Open Access
- 1 June 2009
- journal article
- review article
- Published by Taylor & Francis Ltd in Neuropsychiatric Disease and Treatment
- Vol. 5, 341-354
- https://doi.org/10.2147/ndt.s4234
Abstract
New approaches in the management of insomnia: weighing the advantages of prolonged-release melatonin and synthetic melatoninergic agonists Rüdiger HardelandJohann Friedrich Blumenbach Institute of Zoology and Anthropology, University of Göttingen, Germany Hypnotic effects of melatonin and melatoninergic drugs are mediated via MT1 and MT2 receptors, especially those in the circadian pacemaker, the suprachiasmatic nucleus, which acts on the hypothalamic sleep switch. Therefore, they differ fundamentally from GABAergic hypnotics. Melatoninergic agonists primarily favor sleep initiation and reset the circadian clock to phases allowing persistent sleep, as required in circadian rhythm sleep disorders. A major obstacle for the use of melatonin to support sleep maintenance in primary insomnia results from its short half-life in the circulation. Solutions to this problem have been sought by developing prolonged-release formulations of the natural hormone, or melatoninergic drugs of longer half-life, such as ramelteon, tasimelteon and agomelatine. With all these drugs, improvements of sleep are statistically demonstrable, but remain limited, especially in primary chronic insomnia, so that GABAergic drugs may be indicated. Melatoninergic agonists do not cause next-day hangover and withdrawal effects, or dependence. They do not induce behavioral changes, as sometimes observed with z-drugs. Despite otherwise good tolerability, the use of melatoninergic drugs in children, adolescents, and during pregnancy has been a matter of concern, and should be avoided in autoimmune diseases and Parkinsonism. Problems and limits of melatoninergic hypnotics are compared.Keywords: agomelatine, hypnotics, melatonin, prolonged-release, ramelteon, tasimelteonKeywords
This publication has 101 references indexed in Scilit:
- The pontine REM switch: past and presentThe Journal of Physiology, 2007
- Efficacy of prolonged release melatonin in insomnia patients aged 55–80 years: quality of sleep and next-day alertness outcomesCurrent Medical Research and Opinion, 2007
- Smith-Magenis syndrome: A case report of improved sleep after treatment with β1-adrenergic antagonists and melatoninThe Journal of Pediatrics, 2006
- Age‐related Changes in the Circadian and Homeostatic Regulation of Human SleepChronobiology International, 2006
- A single blind, placebo controlled, across groups dose escalation study of the safety, tolerability, pharmacokinetics and pharmacodynamics of the melatonin analog β-methyl-6-chloromelatoninLife Sciences, 2004
- Double blind randomised placebo controlled trial of low dose melatonin for sleep disorders in dementiaInternational Journal of Geriatric Psychiatry, 2002
- Mammalian melatonin receptors: molecular biology and signal transductionCell and tissue research, 2002
- Circadian Rhythm Sleep DisordersCNS Drugs, 2001
- The Influence of Intravenous L-Tryptophan on Plasma Melatonin and Sleep in MenPharmacopsychiatry, 1991
- Tryptophol, 5-hydroxytryptophol and 5-methoxytryptophol induced sleep in miceLife Sciences, 1970