Ramelteon

Ramelteon
Clinical data
Trade names	Rozerem, others
Other names	TAK-375
AHFS/Drugs.com	Monograph
MedlinePlus	a605038
License data	US DailyMed: Ramelteon;
Dependence; liability	Low
Routes of; administration	By mouth
ATC code	N05CH02 (WHO) ;
Legal status
Legal status	BR: Class C1 (Other controlled substances); US: ℞-only;
Pharmacokinetic data
Bioavailability	1.8%
Protein binding	82% (mainly albumin)
Metabolism	Liver (CYP1A2 major, CYP2C and CYP3A4 minor)
Metabolites	M-II (active metabolite)
Elimination half-life	Ramelteon: 1–2.6 hours; M-II: 2–5 hours
Excretion	Kidney: 84%; Feces: 4%
Identifiers
	IUPAC name (S)-N-[2-(1,6,7,8-tetrahydro-2H-indeno-[5,4-b]; furan-8-yl)ethyl]propionamide;
CAS Number	196597-26-9 ;
PubChem CID	208902;
IUPHAR/BPS	1356;
DrugBank	DB00980 ;
ChemSpider	9033484 ;
UNII	901AS54I69;
KEGG	D02689 ;
ChEMBL	ChEMBL133775 ;
CompTox Dashboard (EPA)	DTXSID6045951 ;
ECHA InfoCard	100.215.666
Chemical and physical data
Formula	C16H21NO2
Molar mass	259.349 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CCC(=O)NCC[C@@H]1CCc2ccc3c(c21)CCO3;
	InChI InChI=1S/C16H21NO2/c1-2-15(18)17-9-7-12-4-3-11-5-6-14-13(16(11)12)8-10-19-14/h5-6,12H,2-4,7-10H2,1H3,(H,17,18)/t12-/m1/s1 ; Key:YLXDSYKOBKBWJQ-GFCCVEGCSA-N ;
	(verify)

Ramelteon, sold under the brand name Rozerem among others, is a melatonin agonist medication which is used in the treatment of insomnia.^[3]^[5] It is indicated specifically for the treatment of insomnia characterized by difficulties with sleep onset.^[3] It reduces the time taken to fall asleep, but the degree of clinical benefit is small.^[6] The medication is approved for long-term use.^[3] Ramelteon is taken by mouth.^[3]

Side effects of ramelteon include somnolence, dizziness, fatigue, nausea, exacerbated insomnia, and changes in hormone levels.^[3] Ramelteon is an analogue of melatonin and is a selective agonist of the melatonin MT₁ and MT₂ receptors.^[3] The half-life and duration of ramelteon are much longer than those of melatonin.^[7] Ramelteon is not a benzodiazepine or Z-drug and does not interact with GABA receptors, instead having a distinct mechanism of action.^[3]^[8]

Ramelteon was first described in 2002^[9] and was approved for medical use in 2005.^[10] Unlike certain other sleep medications, ramelteon is not a controlled substance^{[contradictory]} and has no known potential for misuse.^[3]

^ Kim HK, Yang KI (December 2022). "Melatonin and melatonergic drugs in sleep disorders". Translational and Clinical Pharmacology. 30 (4): 163–171. doi:10.12793/tcp.2022.30.e21. PMC 9810491. PMID 36632077.
^ Anvisa (31 March 2023). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 4 April 2023). Archived from the original on 3 August 2023. Retrieved 16 August 2023.
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o ^p ^q Cite error: The named reference Rozerem FDA label was invoked but never defined (see the help page).
^ Karim A, Tolbert D, Cao C (February 2006). "Disposition kinetics and tolerance of escalating single doses of ramelteon, a high-affinity MT1 and MT2 melatonin receptor agonist indicated for treatment of insomnia". Journal of Clinical Pharmacology. 46 (2): 140–148. doi:10.1177/0091270005283461. PMID 16432265. S2CID 38171735.
^ Neubauer DN (February 2008). "A review of ramelteon in the treatment of sleep disorders". Neuropsychiatric Disease and Treatment. 4 (1): 69–79. doi:10.2147/ndt.s483. PMC 2515902. PMID 18728808.
^ Cite error: The named reference pmid24656909 was invoked but never defined (see the help page).
^ Cite error: The named reference pmid18368944 was invoked but never defined (see the help page).
^ Atkin T, Comai S, Gobbi G (April 2018). "Drugs for Insomnia beyond Benzodiazepines: Pharmacology, Clinical Applications, and Discovery". Pharmacological Reviews. 70 (2): 197–245. doi:10.1124/pr.117.014381. PMID 29487083. S2CID 3578916.
^ Cite error: The named reference pmid12213063 was invoked but never defined (see the help page).
^ Cite error: The named reference FDA2005 was invoked but never defined (see the help page).

[Yang2022-1] Kim HK, Yang KI (December 2022). "Melatonin and melatonergic drugs in sleep disorders". Translational and Clinical Pharmacology. 30 (4): 163–171. doi:10.12793/tcp.2022.30.e21. PMC 9810491. PMID 36632077.

[2] Anvisa (31 March 2023). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 4 April 2023). Archived from the original on 3 August 2023. Retrieved 16 August 2023.

[Rozerem_FDA_label-3] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o ^p ^q Cite error: The named reference Rozerem FDA label was invoked but never defined (see the help page).

[4] Karim A, Tolbert D, Cao C (February 2006). "Disposition kinetics and tolerance of escalating single doses of ramelteon, a high-affinity MT1 and MT2 melatonin receptor agonist indicated for treatment of insomnia". Journal of Clinical Pharmacology. 46 (2): 140–148. doi:10.1177/0091270005283461. PMID 16432265. S2CID 38171735.

[pmid18728808-5] Neubauer DN (February 2008). "A review of ramelteon in the treatment of sleep disorders". Neuropsychiatric Disease and Treatment. 4 (1): 69–79. doi:10.2147/ndt.s483. PMC 2515902. PMID 18728808.

[pmid24656909-6] Cite error: The named reference pmid24656909 was invoked but never defined (see the help page).

[pmid18368944-7] Cite error: The named reference pmid18368944 was invoked but never defined (see the help page).

[pmid29487083-8] Atkin T, Comai S, Gobbi G (April 2018). "Drugs for Insomnia beyond Benzodiazepines: Pharmacology, Clinical Applications, and Discovery". Pharmacological Reviews. 70 (2): 197–245. doi:10.1124/pr.117.014381. PMID 29487083. S2CID 3578916.

[pmid12213063-9] Cite error: The named reference pmid12213063 was invoked but never defined (see the help page).

[FDA2005-10] Cite error: The named reference FDA2005 was invoked but never defined (see the help page).

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