Investigational melatonin receptor agonists - PubMed (original) (raw)
Review
Investigational melatonin receptor agonists
Rüdiger Hardeland. Expert Opin Investig Drugs. 2010 Jun.
Abstract
Importance of the field: Melatonin is a major chronobiological regulator involved in circadian phasing, sleep, and numerous other functions including cyto-/neuroprotection, immune modulation, and energy metabolism. The suitability of melatonin as a drug is limited because of its short half-life. Therefore, various indolic and non-indolic melatonergic agonists have been developed. Frequent health problems such as sleep disturbances, neuropsychiatric disorders related to circadian dysphasing, and metabolic diseases associated with insulin resistance are targeted by melatonergic agonists.
Areas covered in this review: Various synthetic melatonergic drugs are compared with regard to receptor affinities, selectivity, effects on sleep, endogenous melatonin, circadian phase and insulin-related metabolism.
What the reader will gain: The chemical design of melatonin receptor agonists is discussed in relation to consequences for receptor affinity, selectivity, metabolism, and spectrum of effects.
Take home message: Melatonergic agonists are suitable for phase-shifting circadian rhythms, and may be used for treating disorders related to circadian dysfunction including sleep difficulties. Facilitation of sleep onset is a general property, whereas promotion of sleep maintenance is demonstrable but not always fully sufficient. Details are especially available for tasimelteon. Support of insulin sensitivity may become a new area of application for compounds such as NEU-P11. Some drugs acting additionally as serotonergic antagonists display antidepressant properties.
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