Ramelteon

Identification

Name

Ramelteon

Accession Number

DB00980  (APRD01213)

Type

Small Molecule

Groups

Approved, Investigational

Description

Ramelteon is the first in a new class of sleep agents that selectively binds to the melatonin receptors in the suprachiasmatic nucleus (SCN). It is used for insomnia, particularly delayed sleep onset. Ramelteon has not been shown to produce dependence and has shown no potential for abuse.

Structure

3D

Download

MOLSDF3D-SDFPDBSMILESInChI

Similar Structures

Structure for Ramelteon (DB00980)

×

Close

Synonyms

• Ramelteon

External IDs

TAK-375 / TAK375

Product Images

Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Unlock Additional Data
Rozerem	Tablet, film coated	8 mg/1	Oral	Lake Erie Medical Dba Quality Care Produts Llc	2011-05-18	2017-06-01
Rozerem	Tablet, film coated	8 mg/1	Oral	Avera McKennan Hospital	2015-03-05	2018-07-11
Rozerem	Tablet, film coated	8 mg/1	Oral	Rebel Distributors	2005-07-22	Not applicable
Rozerem	Tablet, film coated	8 mg/1	Oral	bryant ranch prepack	2005-07-22	Not applicable
Rozerem	Tablet, film coated	8 mg/1	Oral	Physicians Total Care, Inc.	2006-08-01	Not applicable
Rozerem	Tablet, film coated	8 mg/1	Oral	Takeda Pharmaceuticals America, Inc.	2005-07-22	Not applicable
Rozerem	Tablet, film coated	8 mg/1	Oral	Carilion Materials Management	2005-07-22	Not applicable

Additional Data Available

Application Number
Application Number
A unique ID assigned by the FDA when a product is submitted for approval by the labeller.
Learn more
Product Code
Product Code
A governmentally-recognized ID which uniquely identifies the product within its regulatory market.
Learn more

Generic Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Unlock Additional Data
Ramelteon	Tablet	8 mg/1	Oral	Cadila Healthcare Limited	2019-07-23	Not applicable
Ramelteon	Tablet	8 mg/1	Oral	Zydus Pharmaceuticals (USA) Inc.	2019-07-23	Not applicable
Ramelteon	Tablet	8 mg/1	Oral	Dr.Reddys Laboratories Inc	2019-07-22	Not applicable
Ramelteon	Tablet	8 mg/1	Oral	Golden State Medical Supply	2013-07-26	Not applicable
Ramelteon	Tablet	8 mg/1	Oral	Actavis Pharma, Inc.	2019-07-22	Not applicable
Ramelteon	Tablet, film coated	8 mg/1	Oral	i3 Pharmaceuticals, LLC	2020-04-30	Not applicable
Ramelteon	Tablet	8 mg/1	Oral	bryant ranch prepack	2019-07-22	Not applicable

Additional Data Available

Application Number
Application Number
A unique ID assigned by the FDA when a product is submitted for approval by the labeller.
Learn more
Product Code
Product Code
A governmentally-recognized ID which uniquely identifies the product within its regulatory market.
Learn more

Categories

• Central Nervous System Depressants
• Cytochrome P-450 CYP1A2 Substrates
• Cytochrome P-450 CYP2C19 Substrates
• Cytochrome P-450 CYP2C9 Substrates
• Cytochrome P-450 CYP3A Substrates
• Cytochrome P-450 CYP3A4 Substrates
• Cytochrome P-450 Substrates
• Drugs that are Mainly Renally Excreted
• Hypnotics and Sedatives
• Melatonin Receptor Agonists
• Nervous System
• Psycholeptics

UNII

901AS54I69

CAS number

196597-26-9

Weight

Average: 259.3434
Monoisotopic: 259.157228921

Chemical Formula

C₁₆H₂₁NO₂

InChI Key

YLXDSYKOBKBWJQ-LBPRGKRZSA-N

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-/m0/s1

IUPAC Name

N-{2-[(8S)-1H,2H,6H,7H,8H-indeno[5,4-b]furan-8-yl]ethyl}propanamide

SMILES

CCC(=O)NCC[C@@H]1CCC2=C1C1=C(OCC1)C=C2

Pharmacology

Indication

For the treatment of insomnia characterized by difficulty with sleep onset.

Associated Conditions

• Insomnia

Pharmacodynamics

Ramelteon is the first selective melatonin agonist. It works by mimicking melatonin (MT), a naturally occuring hormone that is produced during the sleep period and thought to be responsible for the regulation of circadian rhythm underlying the normal sleep-wake cycle. Ramelteon has a high affinity for the MT₁ and MT₂ receptors. The MT₁ and MT₂ receptors are located in the brain's suprachiasmatic nuclei (SCN),which is known as the body's "master clock" because it regulates the 24-hour sleep-wake cycle. Ramelteon has an active metabolite that is less potent but circulates in higher concentrations than the parent compound. The metabolite also has weak affinity for the 5HT2b receptor.

Mechanism of action

Ramelteon is a melatonin receptor agonist with both high affinity for melatonin MT₁ and MT₂ receptors, and lower selectivity for the MT₃ receptor. Melatonin production is concurrent with nocturnal sleep, meaning that an increase in melatonin levels is related to the onset of self-reported sleepiness and an increase in sleep propensity. MT₁ receptors are believed to be responsible for regulation of sleepiness and facilitation of sleep onset, and MT₂ receptors are believed to mediate phase-shifting effects of melatonin on the circadian rhythm. While MT₁ and MT₂ receptors are associated with the sleep-wake cycle, MT₃ has a completely different profile, and therefore is not likely to be involved in the sleep-wake cycle. Remelteon has no appreciable affinity for the gamma-aminobutyric acid (GABA) receptor complex or receptors that bind neuropeptides, cytokines, serotonin, dopamine, norepinephrine, acetylcholine, or opiates.

Target	Actions	Organism
AMelatonin receptor type 1A	multitarget	Humans
AMelatonin receptor type 1B	multitarget	Humans

Unlock Additional Data

Additional Data Available

Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

Learn more

Additional Data Available

Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

Learn more

Additional Data Available

Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

Learn more

Absorption

Rapid, total absorption is at least 84%.

Volume of distribution

• 73.6 L

Protein binding

~82% (in human serum)

Metabolism

Hepatic

Route of elimination

Following oral administration of radiolabeled ramelteon, 84% of total radioactivity was excreted in urine and approximately 4% in feces, resulting in a mean recovery of 88%. Less than 0.1% of the dose was excreted in urine and feces as the parent compound.

Half life

~1-2.6 hours

Clearance

Not Available

Toxicity

Not Available

Affected organisms

• Humans and other mammals

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

• All Drugs
• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental

Drug	Interaction
Unlock Additional Data
(R)-warfarin	The metabolism of (R)-warfarin can be decreased when combined with Ramelteon.
(S)-Warfarin	The metabolism of (S)-Warfarin can be decreased when combined with Ramelteon.
2,5-Dimethoxy-4-ethylthioamphetamine	The risk or severity of adverse effects can be increased when Ramelteon is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
4-Bromo-2,5-dimethoxyamphetamine	The risk or severity of adverse effects can be increased when Ramelteon is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-Methoxyamphetamine	The risk or severity of adverse effects can be increased when Ramelteon is combined with 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamine	The risk or severity of adverse effects can be increased when Ramelteon is combined with 5-methoxy-N,N-dimethyltryptamine.
6-O-benzylguanine	The metabolism of 6-O-benzylguanine can be decreased when combined with Ramelteon.
7-Nitroindazole	The risk or severity of adverse effects can be increased when Ramelteon is combined with 7-Nitroindazole.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline	The risk or severity of adverse effects can be increased when Ramelteon is combined with 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline.
8-azaguanine	The metabolism of 8-azaguanine can be decreased when combined with Ramelteon.

Additional Data Available

Extended Description
Extended Description
Extended description of the mechanism of action and particular properties of each drug interaction.
Learn more
Severity
Severity
A severity rating for each drug interaction, from minor to major.
Learn more
Evidence Level
Evidence Level
A rating for the strength of the evidence supporting each drug interaction.
Learn more
Action
Action
An effect category for each drug interaction. Know how this interaction affects the subject drug.
Learn more

Food Interactions

• Avoid alcohol.
• Do not take with or immediately after a high-fat meal.

References

Synthesis Reference

Vinod Kumar Kansal, Dhirenkumar N. Mistry, Sanjay L. Vasoya, "Intermediates and processes for the synthesis of Ramelteon." U.S. Patent US20080242877, issued October 02, 2008.

US20080242877

General References

1. Karim A, Tolbert D, Cao C: Disposition kinetics and tolerance of escalating single doses of ramelteon, a high-affinity MT1 and MT2 melatonin receptor agonist indicated for treatment of insomnia. J Clin Pharmacol. 2006 Feb;46(2):140-8. [PubMed:16432265]
2. Miyamoto M: Pharmacology of ramelteon, a selective MT1/MT2 receptor agonist: a novel therapeutic drug for sleep disorders. CNS Neurosci Ther. 2009 Winter;15(1):32-51. doi: 10.1111/j.1755-5949.2008.00066.x. [PubMed:19228178]
3. Pandi-Perumal SR, Srinivasan V, Spence DW, Moscovitch A, Hardeland R, Brown GM, Cardinali DP: Ramelteon: a review of its therapeutic potential in sleep disorders. Adv Ther. 2009 Jun;26(6):613-26. doi: 10.1007/s12325-009-0041-6. Epub 2009 Jun 30. [PubMed:19568703]
4. Borja NL, Daniel KL: Ramelteon for the treatment of insomnia. Clin Ther. 2006 Oct;28(10):1540-55. [PubMed:17157111]
5. Roth T, Stubbs C, Walsh JK: Ramelteon (TAK-375), a selective MT1/MT2-receptor agonist, reduces latency to persistent sleep in a model of transient insomnia related to a novel sleep environment. Sleep. 2005 Mar;28(3):303-7. [PubMed:16173650]
6. Simpson D, Curran MP: Ramelteon: a review of its use in insomnia. Drugs. 2008;68(13):1901-19. [PubMed:18729542]

External Links

Human Metabolome Database

HMDB0015115

PubChem Compound

208902

PubChem Substance

46505923

ChemSpider

181000

BindingDB

50118470

RxNav

596205

ChEBI

109549

ChEMBL

CHEMBL1218

ZINC

ZINC000003960338

Therapeutic Targets Database

DAP000070

PharmGKB

PA164744896

Guide to Pharmacology

GtP Drug Page

PDBe Ligand

JEV

RxList

RxList Drug Page

Drugs.com

Drugs.com Drug Page

Wikipedia

Ramelteon

ATC Codes

N05CH02 — Ramelteon

• N05CH — Melatonin receptor agonists
• N05C — HYPNOTICS AND SEDATIVES
• N05 — PSYCHOLEPTICS
• N — NERVOUS SYSTEM

PDB Entries

6me2 / 6me9

FDA label

Download (2.36 MB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
1	Completed	Not Available	Insomnia	1
1	Completed	Basic Science	Marijuana Dependence	1
1	Completed	Prevention	Insomnia	1
2	Completed	Prevention	Amnestic / Cognitive Disorders / Delayed Emergence From Anesthesia / Delirium / Delirium, Dementia / Delirium, Dementia, Amnestic, Cognitive Disorders	1
2	Completed	Treatment	Chronic Obstructive Pulmonary Disease (COPD)	1
2	Completed	Treatment	Insomnia Chronic	2
2	Completed	Treatment	OSAS (Obstructive Sleep Apneas Syndrome)	1
2	Completed	Treatment	Sleep Disorder	1
2	Completed	Treatment	Sleep Disorders, Circadian Rhythm	1
2	Completed	Treatment	Sleep Initiation and Maintenance Disorders	2
2	Completed	Treatment	Minor burns / Sleep	1
2	Completed	Treatment	Substance Abuse	1
2	Completed	Treatment	Tobacco Use Disorders	1
2	Terminated	Prevention	Migraine / Migraine With Aura / Migraine Without Aura	1
3	Completed	Treatment	Balance	1
3	Completed	Treatment	Insomnia	1
3	Completed	Treatment	Insomnia Chronic	5
3	Completed	Treatment	Insomnia / OSAS (Obstructive Sleep Apneas Syndrome)	1
3	Completed	Treatment	Sleep Initiation and Maintenance Disorders	2
3	Completed	Treatment	Transient Insomnia	1
3	Terminated	Treatment	Acute Depressive Episode	1
3	Terminated	Treatment	Asthma / Insomnia	1
3	Terminated	Treatment	Bipolar Disorder (BD)	2
3	Terminated	Treatment	Bipolar Disorder (BD) / Insomnia	1
3	Terminated	Treatment	Insomnia Chronic	1
3	Terminated	Treatment	Insomnia / Major Depressive Disorder (MDD)	1
3	Unknown Status	Treatment	Gastro-esophageal Reflux Disease (GERD) / Insomnia Chronic	1
3	Withdrawn	Treatment	Bipolar Disorder (BD)	1
4	Active Not Recruiting	Treatment	Insomnia Chronic	1
4	Completed	Treatment	ADHD With Sleep Onset Insomnia	1
4	Completed	Treatment	Bipolar Disorder (BD)	1
4	Completed	Treatment	Chronic Obstructive Pulmonary Disease (COPD)	1
4	Completed	Treatment	Circadian Dysregulation	1
4	Completed	Treatment	Insomnia	2
4	Completed	Treatment	Insomnia Chronic	2
4	Completed	Treatment	Insomnia / Major Depressive Disorder (MDD)	1
4	Completed	Treatment	Insomnia / Quadriplegia / Sleep disorders and disturbances / Spinal Cord Injuries (SCI)	1
4	Completed	Treatment	Liver Cirrhosis	1
4	Completed	Treatment	REM Sleep Behavior Disorder	1
4	Completed	Treatment	Schizoaffective Disorders / Schizophrenia / Schizophreniform Disorders	1
4	Completed	Treatment	Schizophrenia	1
4	Completed	Treatment	Seasonal Affective Disorder (SAD)	1
4	Completed	Treatment	Sleep Deprivation	1
4	Recruiting	Prevention	Delirium	1
4	Recruiting	Treatment	Delirium	1
4	Recruiting	Treatment	Insomnia	1
4	Terminated	Treatment	Insomnia Chronic	1
4	Terminated	Treatment	Migraine	1
4	Terminated	Treatment	Parkinson's Disease (PD)	1
4	Unknown Status	Treatment	Injuries, Brain / Insomnia	1
4	Unknown Status	Treatment	Insomnia	1
4	Withdrawn	Other	Delirium	1
4	Withdrawn	Prevention	Delirium in Old Age	1
Not Available	Active Not Recruiting	Prevention	Delirium / Sleep Deprivation	1
Not Available	Completed	Not Available	Insomnia	2
Not Available	Completed	Basic Science	Healthy Volunteers	1
Not Available	Completed	Diagnostic	OSAS (Obstructive Sleep Apneas Syndrome)	1
Not Available	Terminated	Treatment	Insomnia / Panic Disorders	1
Not Available	Terminated	Treatment	Pain, Neuropathic	1
Not Available	Terminated	Treatment	Parkinsonism / REM Behavior Disorder	1
Not Available	Withdrawn	Treatment	Circadian Dysregulation / Diffuse Lewy Body Disease / Huntington's Disease (HD) / Parkinson's Disease (PD) / Sleep disorders and disturbances	1

Pharmacoeconomics

Manufacturers

• Takeda global research development center inc

Packagers

• Bryant Ranch Prepack
• DispenseXpress Inc.
• Innoviant Pharmacy Inc.
• Physicians Total Care Inc.
• Rebel Distributors Corp.
• Southwood Pharmaceuticals
• Takeda Pharmaceutical Co. Ltd.

Dosage forms

Form	Route	Strength
Tablet	Oral	8 mg/1
Tablet, film coated	Oral	8 mg/1

Prices

Unit description	Cost	Unit
Rozerem 8 mg tablet	5.17USD	tablet

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)
Unlock Additional Data
US6034239	No	2000-03-07	2019-07-22
US10098866	No	2018-10-16	2021-11-16

Additional Data Available

Filed On
Filed On
The date on which a patent was filed with the relevant government.
Learn more

Properties

State

Solid

Experimental Properties

Property	Value	Source
logP	2.4	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	0.0164 mg/mL	ALOGPS
logP	3.03	ALOGPS
logP	2.57	ChemAxon
logS	-4.2	ALOGPS
pKa (Strongest Acidic)	15.82	ChemAxon
pKa (Strongest Basic)	-0.4	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	2	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	38.33 Å2	ChemAxon
Rotatable Bond Count	4	ChemAxon
Refractivity	75.52 m3·mol-1	ChemAxon
Polarizability	29.99 Å3	ChemAxon
Number of Rings	3	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	No	ChemAxon

Predicted ADMET features

Property	Value	Probability
Human Intestinal Absorption	+	1.0
Blood Brain Barrier	+	0.9934
Caco-2 permeable	+	0.5893
P-glycoprotein substrate	Substrate	0.5211
P-glycoprotein inhibitor I	Non-inhibitor	0.8548
P-glycoprotein inhibitor II	Non-inhibitor	0.7877
Renal organic cation transporter	Non-inhibitor	0.6381
CYP450 2C9 substrate	Non-substrate	0.7876
CYP450 2D6 substrate	Non-substrate	0.6392
CYP450 3A4 substrate	Substrate	0.512
CYP450 1A2 substrate	Inhibitor	0.7314
CYP450 2C9 inhibitor	Non-inhibitor	0.6471
CYP450 2D6 inhibitor	Non-inhibitor	0.5916
CYP450 2C19 inhibitor	Inhibitor	0.8314
CYP450 3A4 inhibitor	Non-inhibitor	0.9196
CYP450 inhibitory promiscuity	High CYP Inhibitory Promiscuity	0.7763
Ames test	Non AMES toxic	0.7016
Carcinogenicity	Non-carcinogens	0.8206
Biodegradation	Ready biodegradable	0.6635
Rat acute toxicity	2.1034 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.7898
hERG inhibition (predictor II)	Inhibitor	0.5

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted GC-MS Spectrum - GC-MS	Predicted GC-MS	Not Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
MS/MS Spectrum - , positive	LC-MS/MS	splash10-0nmi-2980000000-5ee1e7ec83e5c4578dfe

Taxonomy

Description

This compound belongs to the class of organic compounds known as indanes. These are compounds containing an indane moiety, which consists of a cyclopentane fused to a benzene ring.

Kingdom

Organic compounds

Super Class

Benzenoids

Class

Indanes

Sub Class

Not Available

Direct Parent

Indanes

Alternative Parents

Coumarans / Alkyl aryl ethers / Secondary carboxylic acid amides / Oxacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds

Substituents

Indane / Coumaran / Alkyl aryl ether / Carboxamide group / Secondary carboxylic acid amide / Oxacycle / Organoheterocyclic compound / Ether / Carboxylic acid derivative / Hydrocarbon derivative

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

Not Available

×

Unlock Data

There is additional data available for commercial users including Adverse Effects, Contraindications, and Blackbox Warnings. Contact us to learn more about these and other features.

Learn more

Drug created on June 13, 2005 07:24 / Updated on May 02, 2020 03:23