Ramelteon

Summary

Ramelteon (CHEMBL1218) is an approved small molecule (ATC N05CH02) targeting MTNR1A and MTNR1B; indicated across 13 conditions including insomnia and sleep disorder.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: N05CH02
• Targets: 2 (MTNR1A, MTNR1B)
• Indications: 13 conditions
• Clinical trials: 72
• Chemistry: 259.34 Da · C16H21NO2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1218
Name	Ramelteon
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	208902
ATC	N05CH02
Molecular formula	C16H21NO2
Molecular weight	259.34
InChIKey	YLXDSYKOBKBWJQ-LBPRGKRZSA-N

SMILES: CCC(=O)NCC[C@@H]1CCC2=C1C3=C(C=C2)OCC3

IUPAC name: N-[2-[(8S)-2,6,7,8-tetrahydro-1H-cyclopenta[e][1]benzofuran-8-yl]ethyl]propanamide

Also known as: Ramelteon, Rozerem, TAK-375, TAK375, RAMELTEON, RamelteonÊ, RamelteonÂ, ramelteon

Patent coverage: 1,424 distinct patent families (5,217 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 5,202 (100%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
MTNR1A	MT1 receptor	Full agonist	10.9	0%	P48039
MTNR1B	MT2 receptor	Full agonist	10	0.2%	P49286

Broader ChEMBL bioactivity targets: 5 (assay-derived). Sample: Melatonin receptor type 1A, Melatonin receptor type 1B, Melatonin receptor, Sigma non-opioid intracellular receptor 1, Bile salt export pump.

Bioactivity

ChEMBL activities: 6 potent at pChembl ≥ 5 of 7 total. Top 100 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
MTNR1A	10.86	Ki	0.01	nM	CHEMBL_ACT_895415
MTNR1A	10.86	Ki	0.01	nM	CHEMBL_ACT_895419
MTNR1A	10.85	Ki	0.01	nM	CHEMBL_ACT_23270156
MTNR1B	10.35	Ki	0.04	nM	CHEMBL_ACT_895418
MTNR1B	9.95	Ki	0.11	nM	CHEMBL_ACT_23270157
SIGMAR1	5.05	Ki	8846	nM	CHEMBL_ACT_25741629

Target pathways

Aggregated over 2 target gene(s): MTNR1A, MTNR1B.

Top Reactome pathways

6 total, by targets touching each:

Pathway	Targets	Genes
Signal Transduction	2	MTNR1A, MTNR1B
Signaling by GPCR	2	MTNR1A, MTNR1B
Class A/1 (Rhodopsin-like receptors)	2	MTNR1A, MTNR1B
GPCR downstream signalling	2	MTNR1A, MTNR1B
G alpha (i) signalling events	2	MTNR1A, MTNR1B
GPCR ligand binding	2	MTNR1A, MTNR1B

Dominant GO biological processes

GO term	Targets
G protein-coupled receptor signaling pathway	2
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	2
signal transduction	2
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	1
mating behavior	1
circadian rhythm	1
chemical synaptic transmission	1
negative regulation of receptor guanylyl cyclase signaling pathway	1
glucose homeostasis	1
camera-type eye development	1
negative regulation of neuron apoptotic process	1
negative regulation of vasoconstriction	1
positive regulation of circadian sleep/wake cycle, non-REM sleep	1
negative regulation of insulin secretion	1
regulation of insulin secretion	1

Indications & clinical

Indications

1 approved indication. FDA phase 4, plus an anticancer drug’s labelled cancer uses (which ChEMBL often logs at phase 3).

Indication	Phase	MONDO	EFO
insomnia	4	MONDO:0013600	EFO:0004698

12 diseases in clinical trials (phase 1–3, investigational — not approved indications). Highest ChEMBL trial phase per disease; a non-cancer approved use is occasionally logged at phase 3 here.

Disease (in trials)	Phase	MONDO	EFO
sleep disorder	3	MONDO:0100081	EFO:0008568
depressive disorder	3	MONDO:0002050	MONDO:0002050
bipolar disorder	3	MONDO:0004985	MONDO:0004985
nicotine dependence	2	MONDO:0008575	EFO:0003768
chronic obstructive pulmonary disease	2	MONDO:0005002	EFO:0000341
drug dependence	2	MONDO:0005303	EFO:0003890
obstructive sleep apnea syndrome	2	MONDO:0007147	EFO:0003918
burn	2	MONDO:0043519	EFO:0009516
severe acute respiratory syndrome	2	MONDO:0005091	MONDO:0100096
migraine with aura	2	MONDO:0005475	MONDO:0005475
migraine without aura	2	MONDO:0100431	MONDO:0100431
cannabis dependence	1	MONDO:0005689	EFO:0007191

Clinical trials

Total trials: 72.

Phase distribution

Phase	Trials
PHASE4	30
PHASE3	18
PHASE2	12
Not specified	9
PHASE1	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05069428	PHASE4	RECRUITING	Delirium Reduction With Ramelteon
NCT07598734	PHASE4	NOT_YET_RECRUITING	Doxepin Alone or Combined With Ramelteon Versus Placebo for Improving Sleep Quality After Primary Total Knee Arthroplasty
NCT00316992	PHASE4	COMPLETED	Safety of Ramelteon in Subjects With Chronic Obstructive Pulmonary Disease
NCT00337272	PHASE4	TERMINATED	Treating Chronic Insomnia in Breast Cancer Patients
NCT00391755	PHASE4	TERMINATED	A Double-Blind Placebo-Controlled Trial of Rozerem in Migraine Headaches
NCT00414102	PHASE4	COMPLETED	Subjective Efficacy of Ramelteon on Sleep in Adults With Chronic Insomnia.
NCT00462254	PHASE4	TERMINATED	Ramelteon (ROZEREM) in the Treatment of Sleep Disturbances Associated With Parkinson’s Disease
NCT00492011	PHASE4	COMPLETED	Efficacy of Ramelteon on Insomnia Symptoms Associated With Jet Lag in Healthy Adult Volunteers
NCT00492232	PHASE4	COMPLETED	Facilitation of Zolpidem (≥10 mg) Discontinuation Through Use of Ramelteon in Subjects With Chronic Insomnia
NCT00502320	PHASE4	COMPLETED	Ramelteon in the Treatment of Sleep and Mood in Patients With Seasonal Affective Disorder
NCT00507546	PHASE4	COMPLETED	Functional Melatonin Replacement for Sleep Disruptions in Individuals With Tetraplegia
NCT00552760	PHASE4	COMPLETED	Ramelteon for the Treatment of Insomnia and Mood Stability in Patients With Euthymic Bipolar Disorder
NCT00576927	PHASE4	COMPLETED	Improving Sleep in Nursing Homes
NCT00595504	PHASE4	COMPLETED	Ramelteon as an Adjunct Therapy in Non-Diabetic Patients With Schizophrenia
NCT00622427	PHASE4	COMPLETED	Ramelteon for Treatment of Adult Patients With ADHD-Related Insomnia
NCT01180855	PHASE4	UNKNOWN	Effects of Ramelteon (8mg) Alone and in Combination With Multi-Component Behavioral Therapy on Sleep and Circadian Phase in Patients With Chronic Insomnia
NCT01207050	PHASE4	UNKNOWN	Effect of Rozerem on Sleep Among People With Traumatic Brain Injury
NCT01401413	PHASE4	COMPLETED	Study to Determine Whether Ramelteon Helps People With REM Sleep Behavior Disorder
NCT02156271	PHASE4	COMPLETED	Mechanisms of Sleep Latency and Health: The Effect of a Melatonin Receptor Agonist in Inflammation and Insulin Resistance
NCT02564939	PHASE4	UNKNOWN	Ramelteon Prevention of Delirium - RCT
NCT02669082	PHASE4	COMPLETED	The Exploratory Study to Investigate the Effect of Ramelteon for Insomnia Patients With Major Depressive Disorder by Using Actigraphy
NCT02840591	PHASE4	WITHDRAWN	Ramelteon and Citicoline for Delirium
NCT03075657	PHASE4	COMPLETED	Study of add-on Ramelteon Therapy on Sleep and Circadian Rhythm Disruption in Patients With Schizophrenia
NCT03091738	PHASE4	COMPLETED	Ramelteon for Treatment of Insomnia in Cirrhosis
NCT03165695	PHASE4	WITHDRAWN	Ramelteon vs Placebo for Prevention of Delirium and Improvement of Sleep in Hospitalized Older Adults
NCT03265951	PHASE4	WITHDRAWN	Ramelteon for Complex Insomnia in Veterans With PTSD
NCT03461042	PHASE4	COMPLETED	The Study of Combination Use of Melatonin Receptor Agonist for Dose Reduction or Interruptions of Benzodiazepine (BZD) and Non-BZD Hypnotics on Chronic Insomnia
NCT03931070	PHASE4	COMPLETED	The Effect of Ramelteon on Delirium and Sleep in Patients Admitted to the ICU
NCT05414864	PHASE4	TERMINATED	Insomnia Prevalence and Treatment Impact on Systemic Hypertension
NCT07382843	PHASE4	COMPLETED	Melatonin Agonist for Shift-time Workers.
NCT06512363	PHASE3	NOT_YET_RECRUITING	A Study of Ramelteon in Chinese Patients With Chronic Insomnia
NCT00237497	PHASE3	COMPLETED	Safety and Efficacy of Ramelteon in Adults With Chronic Insomnia
NCT00247390	PHASE3	COMPLETED	Long-Term Efficacy and Safety of Ramelteon in Adults With Chronic Insomnia.
NCT00585208	PHASE3	TERMINATED	Add-On Ramelteon in Bipolar I Disorder With Clinically Significant Sleep Disturbance
NCT00642694	PHASE3	TERMINATED	Time to Remission of Depressive Symptoms With Combined SSRI and Ramelteon
NCT00656994	PHASE3	COMPLETED	Long-Term Efficacy of Ramelteon on Endocrine Function in Adult Subjects With Chronic Insomnia
NCT00671086	PHASE3	COMPLETED	Efficacy of Ramelteon in Subjects With Chronic Insomnia
NCT00671125	PHASE3	COMPLETED	Study of Efficacy of Ramelteon in Adults With Chronic Insomnia
NCT00671255	PHASE3	COMPLETED	Safety and Efficacy of Ramelteon in Elderly Subjects With Chronic Insomnia
NCT00671294	PHASE3	COMPLETED	Safety and Efficacy of Ramelteon in Elderly Subjects With Chronic Insomnia.
NCT00671398	PHASE3	COMPLETED	Efficacy of Ramelteon on Transient Insomnia in Healthy Adults
NCT00671567	PHASE3	COMPLETED	Ramelteon in Adults With Chronic Insomnia
NCT00672724	PHASE3	TERMINATED	Efficacy of Ramelteon in Adults With Chronic Insomnia
NCT00756002	PHASE3	COMPLETED	Safety and Efficacy Study of Ramelteon in Subjects With Chronic Insomnia
NCT00869167	PHASE3	TERMINATED	Ramelteon for Insomnia Comorbid With Asthma
NCT01048242	PHASE3	COMPLETED	Treatment of Insomnia in Elderly Sleep Apnea Patients With Ramelteon (TAK 375)
NCT01128582	PHASE3	UNKNOWN	Effect of Rozerem on the Perception of GERD Symptoms in Patients With Chronic Insomnia.
NCT01677182	PHASE3	TERMINATED	Safety and Efficacy Study of Ramelteon (TAK-375) Tablets for Sublingual Administration (SL) in Adults With Bipolar 1 Disorder
NCT00325728	PHASE2	COMPLETED	Efficacy and Safety of Ramelteon in Subjects With Mild to Moderate Alzheimer’s Disease
NCT00539110	PHASE2	COMPLETED	Differential Effects of Zolpidem Versus Ramelteon in Burned Children
NCT00593736	PHASE2	COMPLETED	Efficacy of Ramelteon on Speeding Up Sleep in Subjects With Delayed Sleep Phase Syndrome
NCT00671190	PHASE2	COMPLETED	Safety and Efficacy of Ramelteon in Healthy Subjects
NCT00672802	PHASE2	COMPLETED	Safety of Ramelteon in Subjects With Mild to Moderate Chronic Obstructive Pulmonary Disease
NCT00739024	PHASE2	TERMINATED	A Study of a Melatonin Receptor Agonist to Prevent Migraine
NCT00755495	PHASE2	COMPLETED	Safety and Efficacy of Ramelteon and Doxepin in Subjects With Chronic Insomnia
NCT00755508	PHASE2	COMPLETED	Efficacy and Safety of Ramelteon Combined With Gabapentin in Treating Patients With Insomnia
NCT00915135	PHASE2	COMPLETED	Efficacy and Safety of Ramelteon on Chronic Insomnia
NCT02324153	PHASE2	COMPLETED	Ramelteon in the Prevention of Post-operative Delirium
NCT02560324	PHASE2	COMPLETED	Effect of Ramelteon on Smoking Abstinence
NCT04470297	PHASE2	UNKNOWN	Melatonin Agonist on Hospitalized Patients With Confirmed or Suspected COVID-19
NCT00319215	PHASE1	COMPLETED	Effects of Ramelteon on Driving Ability
NCT00893269	PHASE1	COMPLETED	The Effect of Marijuana and Prescription Medications in Mood, Performance and Sleep
NCT00914862	PHASE1	COMPLETED	Pharmacokinetic and Safety of Ramelteon Between Adolescents With Insomnia and Healthy Adults
NCT00595075	Not specified	COMPLETED	Ramelteon for a Nap Prior to a Night Shift
NCT00745030	Not specified	TERMINATED	Efficacy and Tolerability of Ramelteon in Patients With Rapid Eye Movement (REM) Behavior Disorder and Parkinsonism
NCT00746239	Not specified	TERMINATED	Ramelteon for Sleep Initiation Insomnia in Individuals With Panic Disorder Who Are Also on Escitalopram for Anxiety
NCT00753623	Not specified	TERMINATED	Clinical Management of Neuropathic Pain With Ramelteon
NCT00811746	Not specified	COMPLETED	Hypnotics to Improve Polysomnography Yield: Eszopiclone vs Ramelteon?
NCT00907595	Not specified	WITHDRAWN	Treating Sleep/Wake Cycle Disturbances in Basal Ganglia Disorders With Ramelteon
NCT02058992	Not specified	COMPLETED	Ramelteon Tablets 8mg Drug Use Surveillance: Survey on Insomnia Associated With Sleep-onset Difficulty
NCT02153086	Not specified	COMPLETED	Ramelteon 8 mg Tablets Specified Drug-use Survey: - Transitional Survey From the Preceding Drug-use Survey -
NCT02691013	Not specified	UNKNOWN	The Impact of Ramelteon on Sleep and Delirium in Patients Who Undergo Pulmonary Thromboendarterectomy (PTE) Surgery

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

6 molecules share ≥1 primary target. Top 6 by shared-target count:

Molecule	Source	Status	Shared targets
AGOMELATINE	ChEMBL	Phase 4 (approved)	MTNR1A, MTNR1B
CIANIDANOL	ChEMBL	Phase 4 (approved)	MTNR1A, MTNR1B
DOPAMINE	ChEMBL	Phase 4 (approved)	MTNR1A, MTNR1B
MELATONIN	ChEMBL	Phase 4 (approved)	MTNR1A, MTNR1B
MEBUFOTENIN	ChEMBL	Phase 2	MTNR1A, MTNR1B
TASIMELTEON	ChEMBL + PubChem	Phase 4 (approved)	MTNR1B