Ramelteon
[CAS# 196597-26-9]

Identification

• Classification: Biochemical >> Inhibitor >> G protein coupled receptor(GPCR & G Protein) >> MT receptor agonist
• Name: Ramelteon
• Synonyms: (S)-N-[2-(1,6,7,8-Tetrahydro-2H-indeno-[5,4-b]furan-8-yl)ethyl]propionamide
• Molecular Formula: C₁₆H₂₁NO₂
• Molecular Weight: 259.34
• CAS Registry Number: 196597-26-9
• EC Number: 688-929-3
• SMILES: CCC(=O)NCC[C@@H]1CCC2=C1C3=C(C=C2)OCC3

Properties

• Solubility: >30 mg/mL (water)

Safety Data

• Hazard Symbols: GHS07;GHS08 Warning
• Risk Statements: H302-H361
• Safety Statements: P203-P264-P270-P280-P301+P317-P318-P330-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Reproductive toxicity	Repr.	2	H361

Discovery and Applications

Ramelteon is a melatonin receptor agonist that is primarily used to treat insomnia. The discovery of ramelteon stems from the need for safer and more effective insomnia treatments. Traditional sleep medications, such as benzodiazepines and non-benzodiazepine hypnotics, carry the risk of dependence and adverse reactions. Researchers aimed to develop a compound that could mimic the natural sleep-promoting hormone melatonin while avoiding these risks. Ramelteon was developed by Takeda Pharmaceuticals and approved by the FDA in 2005. Its structure is similar to melatonin and selectively targets melatonin receptors MT1 and MT2 in the brain. By acting on these receptors, ramelteon helps synchronize the body's circadian rhythm with the light-dark cycle of the environment, promoting natural sleep onset.

Ramelteon is primarily used for insomnia patients who have trouble falling asleep. It helps regulate the sleep-wake cycle by enhancing the effects of melatonin, which is naturally involved in sleep induction. Unlike many other sleep medications, ramelteon has no risk of dependence or withdrawal and is suitable for long-term use. This advantage is particularly beneficial for patients suffering from chronic insomnia.

Ramelteon has shown efficacy in treating circadian rhythm sleep disorders, such as shift work sleep disorder, and can help individuals adjust to altered sleep schedules. It helps adjust to nontraditional work hours and improves sleep quality and alertness. Ramelteon can also be used to mitigate the effects of jet lag by resetting the body's internal clock, thereby reducing sleep disturbances and daytime fatigue after rapid time zone changes.

In research, ramelteon serves as a tool to study circadian biology and the role of melatonin receptors in sleep regulation. Its specific receptor activity provides insights into the mechanisms that control circadian rhythms and sleep-wake patterns. The development of ramelteon has paved the way for the design of other receptor-specific drugs. Its success has encouraged further exploration of melatonin receptor agonists for the treatment of sleep disorders and other potential circadian rhythm-related disorders.

Emerging research suggests that ramelteon may have potential applications in neuropsychiatric disorders, such as depression and bipolar disorder, where circadian rhythm disturbances are common. Its ability to modulate circadian rhythms could provide therapeutic efficacy in these conditions. Ramelteon is being explored as an adjunctive therapy in combination with other medications to improve sleep quality in patients with complex medical conditions, including chronic pain and neurological disorders.

References

2024. Preventive Effects of Ramelteon, Suvorexant, and Lemborexant on Delirium in Hospitalized Patients With Physical Disease: A Retrospective Cohort Study. Journal of Clinical Psychopharmacology, 44(4).
DOI: 10.1097/jcp.0000000000001876

2024. Ramelteon protects against social defeat stress-associated abnormal behaviors. Pharmacology, biochemistry, and behavior, 241.
DOI: 10.1016/j.pbb.2024.173794

2024. Managing non-24-hour sleep-wake rhythm disorder with ramelteon in a 12-year-old girl with Pierre Robin sequence and developmental delay: a case report. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, 20(6).
DOI: 10.5664/jcsm.11048