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Identification
NameRamelteon
Accession NumberDB00980  (APRD01213)
TypeSmall Molecule
GroupsApproved, Investigational
DescriptionRamelteon 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
Thumb
Synonyms
Rozerem
External Identifiers
  • TAK-375
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
RozeremTablet, film coated8 mg/1OralRebel Distributors Corp2005-07-22Not applicableUs
RozeremTablet, film coated8 mg/1OralTakeda Pharmaceuticals America, Inc.2005-07-22Not applicableUs
RozeremTablet, film coated8 mg/1OralLake Erie Medical DBA Quality Care Products LLC2011-05-18Not applicableUs
RozeremTablet, film coated8 mg/1OralAvera Mc Kennan Hospital2015-03-05Not applicableUs
RozeremTablet, film coated8 mg/1OralPhysicians Total Care, Inc.2006-08-01Not applicableUs
RozeremTablet, film coated8 mg/1Oralbryant ranch prepack2005-07-22Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNII901AS54I69
CAS number196597-26-9
WeightAverage: 259.3434
Monoisotopic: 259.157228921
Chemical FormulaC16H21NO2
InChI KeyYLXDSYKOBKBWJQ-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
IndicationFor the treatment of insomnia characterized by difficulty with sleep onset.
Structured Indications
PharmacodynamicsRamelteon 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 actionRamelteon 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.
TargetKindPharmacological actionActionsOrganismUniProt ID
Melatonin receptor type 1BProteinyes
multitarget
HumanP49286 details
Melatonin receptor type 1AProteinyes
multitarget
HumanP48039 details
Related Articles
AbsorptionRapid, total absorption is at least 84%.
Volume of distribution
  • 73.6 L
Protein binding~82% (in human serum)
Metabolism

Hepatic

Route of eliminationFollowing 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
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Interactions
Drug Interactions
DrugInteractionDrug group
1,1,1,2 TetrafluoroethaneThe risk or severity of adverse effects can be increased when Ramelteon is combined with 1,1,1,2 Tetrafluoroethane.Investigational
7-NitroindazoleThe risk or severity of adverse effects can be increased when 7-Nitroindazole is combined with Ramelteon.Experimental
AbirateroneThe serum concentration of Ramelteon can be increased when it is combined with Abiraterone.Approved
AcepromazineThe risk or severity of adverse effects can be increased when Acepromazine is combined with Ramelteon.Approved, Vet Approved
AceprometazineThe risk or severity of adverse effects can be increased when Aceprometazine is combined with Ramelteon.Approved
adipiplonThe risk or severity of adverse effects can be increased when adipiplon is combined with Ramelteon.Investigational
AgomelatineThe risk or severity of adverse effects can be increased when Agomelatine is combined with Ramelteon.Approved, Investigational
AlfaxaloneThe risk or severity of adverse effects can be increased when Alfaxalone is combined with Ramelteon.Vet Approved
AlfentanilThe risk or severity of adverse effects can be increased when Alfentanil is combined with Ramelteon.Approved, Illicit
AlphacetylmethadolThe risk or severity of adverse effects can be increased when Alphacetylmethadol is combined with Ramelteon.Experimental, Illicit
AlprazolamThe risk or severity of adverse effects can be increased when Alprazolam is combined with Ramelteon.Approved, Illicit, Investigational
AmiodaroneThe serum concentration of Ramelteon can be increased when it is combined with Amiodarone.Approved, Investigational
AmisulprideThe risk or severity of adverse effects can be increased when Amisulpride is combined with Ramelteon.Approved, Investigational
AmitriptylineThe risk or severity of adverse effects can be increased when Amitriptyline is combined with Ramelteon.Approved
AmobarbitalThe risk or severity of adverse effects can be increased when Amobarbital is combined with Ramelteon.Approved, Illicit
AmoxapineThe risk or severity of adverse effects can be increased when Amoxapine is combined with Ramelteon.Approved
AmperozideThe risk or severity of adverse effects can be increased when Amperozide is combined with Ramelteon.Experimental
AprepitantThe serum concentration of Ramelteon can be increased when it is combined with Aprepitant.Approved, Investigational
AripiprazoleThe risk or severity of adverse effects can be increased when Aripiprazole is combined with Ramelteon.Approved, Investigational
ArmodafinilThe metabolism of Ramelteon can be decreased when combined with Armodafinil.Approved, Investigational
ArticaineThe risk or severity of adverse effects can be increased when Articaine is combined with Ramelteon.Approved
AsenapineThe risk or severity of adverse effects can be increased when Asenapine is combined with Ramelteon.Approved
AtazanavirThe serum concentration of Ramelteon can be increased when it is combined with Atazanavir.Approved, Investigational
AtomoxetineThe metabolism of Ramelteon can be decreased when combined with Atomoxetine.Approved
AzaperoneThe risk or severity of adverse effects can be increased when Azaperone is combined with Ramelteon.Vet Approved
AzelastineRamelteon may increase the central nervous system depressant (CNS depressant) activities of Azelastine.Approved
AzelastineThe risk or severity of adverse effects can be increased when Azelastine is combined with Ramelteon.Approved
AzithromycinThe metabolism of Ramelteon can be decreased when combined with Azithromycin.Approved
BaclofenThe risk or severity of adverse effects can be increased when Baclofen is combined with Ramelteon.Approved
BarbitalThe risk or severity of adverse effects can be increased when Barbital is combined with Ramelteon.Illicit
BenperidolThe risk or severity of adverse effects can be increased when Ramelteon is combined with Benperidol.Investigational
BenzocaineThe risk or severity of adverse effects can be increased when Benzocaine is combined with Ramelteon.Approved
Benzyl alcoholThe risk or severity of adverse effects can be increased when Benzyl alcohol is combined with Ramelteon.Approved
BexaroteneThe serum concentration of Ramelteon can be decreased when it is combined with Bexarotene.Approved, Investigational
BoceprevirThe serum concentration of Ramelteon can be increased when it is combined with Boceprevir.Approved
BortezomibThe metabolism of Ramelteon can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Ramelteon can be decreased when it is combined with Bosentan.Approved, Investigational
BrexpiprazoleThe risk or severity of adverse effects can be increased when Ramelteon is combined with Brexpiprazole.Approved
BrimonidineThe risk or severity of adverse effects can be increased when Brimonidine is combined with Ramelteon.Approved
BrimonidineBrimonidine may increase the central nervous system depressant (CNS depressant) activities of Ramelteon.Approved
BromazepamThe risk or severity of adverse effects can be increased when Bromazepam is combined with Ramelteon.Approved, Illicit
BrompheniramineThe risk or severity of adverse effects can be increased when Brompheniramine is combined with Ramelteon.Approved
BrotizolamThe risk or severity of adverse effects can be increased when Brotizolam is combined with Ramelteon.Approved, Withdrawn
BupivacaineThe risk or severity of adverse effects can be increased when Bupivacaine is combined with Ramelteon.Approved, Investigational
BuprenorphineRamelteon may increase the central nervous system depressant (CNS depressant) activities of Buprenorphine.Approved, Illicit, Investigational, Vet Approved
BuspironeThe risk or severity of adverse effects can be increased when Buspirone is combined with Ramelteon.Approved, Investigational
ButabarbitalThe risk or severity of adverse effects can be increased when Butabarbital is combined with Ramelteon.Approved, Illicit
ButacaineThe risk or severity of adverse effects can be increased when Butacaine is combined with Ramelteon.Vet Approved
ButalbitalThe risk or severity of adverse effects can be increased when Butalbital is combined with Ramelteon.Approved, Illicit
ButambenThe risk or severity of adverse effects can be increased when Butamben is combined with Ramelteon.Approved
ButethalThe risk or severity of adverse effects can be increased when Butethal is combined with Ramelteon.Approved, Illicit
ButorphanolThe risk or severity of adverse effects can be increased when Butorphanol is combined with Ramelteon.Approved, Illicit, Vet Approved
CaffeineThe metabolism of Ramelteon can be decreased when combined with Caffeine.Approved
CapecitabineThe serum concentration of Ramelteon can be increased when it is combined with Capecitabine.Approved, Investigational
CarbamazepineThe metabolism of Ramelteon can be increased when combined with Carbamazepine.Approved, Investigational
CarbinoxamineThe risk or severity of adverse effects can be increased when Carbinoxamine is combined with Ramelteon.Approved
CarfentanilThe risk or severity of adverse effects can be increased when Carfentanil is combined with Ramelteon.Illicit, Vet Approved
CarisoprodolThe risk or severity of adverse effects can be increased when Carisoprodol is combined with Ramelteon.Approved
CeritinibThe serum concentration of Ramelteon can be increased when it is combined with Ceritinib.Approved
CetirizineThe risk or severity of adverse effects can be increased when Cetirizine is combined with Ramelteon.Approved
Chloral hydrateThe risk or severity of adverse effects can be increased when Chloral hydrate is combined with Ramelteon.Approved, Illicit, Vet Approved
ChloramphenicolThe metabolism of Ramelteon can be decreased when combined with Chloramphenicol.Approved, Vet Approved
ChlordiazepoxideThe risk or severity of adverse effects can be increased when Chlordiazepoxide is combined with Ramelteon.Approved, Illicit
ChlormezanoneThe risk or severity of adverse effects can be increased when Chlormezanone is combined with Ramelteon.Approved, Withdrawn
ChloroprocaineThe risk or severity of adverse effects can be increased when Chloroprocaine is combined with Ramelteon.Approved
ChlorphenamineThe risk or severity of adverse effects can be increased when Ramelteon is combined with Chlorphenamine.Approved
ChlorpromazineThe risk or severity of adverse effects can be increased when Chlorpromazine is combined with Ramelteon.Approved, Vet Approved
ChlorprothixeneThe risk or severity of adverse effects can be increased when Chlorprothixene is combined with Ramelteon.Approved, Withdrawn
ChlorzoxazoneThe risk or severity of adverse effects can be increased when Chlorzoxazone is combined with Ramelteon.Approved
CholecalciferolThe metabolism of Ramelteon can be decreased when combined with Cholecalciferol.Approved, Nutraceutical
CimetidineThe metabolism of Ramelteon can be decreased when combined with Cimetidine.Approved
CinchocaineThe risk or severity of adverse effects can be increased when Cinchocaine is combined with Ramelteon.Approved, Vet Approved
CitalopramThe metabolism of Ramelteon can be decreased when combined with Citalopram.Approved
ClarithromycinThe serum concentration of Ramelteon can be increased when it is combined with Clarithromycin.Approved
ClemastineThe metabolism of Ramelteon can be decreased when combined with Clemastine.Approved
ClidiniumThe risk or severity of adverse effects can be increased when Clidinium is combined with Ramelteon.Approved
ClobazamThe risk or severity of adverse effects can be increased when Clobazam is combined with Ramelteon.Approved, Illicit
clomethiazoleThe risk or severity of adverse effects can be increased when clomethiazole is combined with Ramelteon.Investigational
ClomipramineThe risk or severity of adverse effects can be increased when Ramelteon is combined with Clomipramine.Approved, Vet Approved
ClonazepamThe risk or severity of adverse effects can be increased when Ramelteon is combined with Clonazepam.Approved, Illicit
ClonidineThe risk or severity of adverse effects can be increased when Clonidine is combined with Ramelteon.Approved
ClorazepateThe risk or severity of adverse effects can be increased when Clorazepate is combined with Ramelteon.Approved, Illicit
ClotrimazoleThe metabolism of Ramelteon can be decreased when combined with Clotrimazole.Approved, Vet Approved
ClozapineThe risk or severity of adverse effects can be increased when Clozapine is combined with Ramelteon.Approved
CobicistatThe serum concentration of Ramelteon can be increased when it is combined with Cobicistat.Approved
CocaineThe risk or severity of adverse effects can be increased when Cocaine is combined with Ramelteon.Approved, Illicit
CodeineThe risk or severity of adverse effects can be increased when Codeine is combined with Ramelteon.Approved, Illicit
ConivaptanThe serum concentration of Ramelteon can be increased when it is combined with Conivaptan.Approved, Investigational
CrizotinibThe metabolism of Ramelteon can be decreased when combined with Crizotinib.Approved
CyclizineThe risk or severity of adverse effects can be increased when Ramelteon is combined with Cyclizine.Approved
CyclobenzaprineThe risk or severity of adverse effects can be increased when Cyclobenzaprine is combined with Ramelteon.Approved
CyclosporineThe metabolism of Ramelteon can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
CyproheptadineThe risk or severity of adverse effects can be increased when Cyproheptadine is combined with Ramelteon.Approved
Cyproterone acetateThe serum concentration of Ramelteon can be decreased when it is combined with Cyproterone acetate.Approved, Investigational
DabrafenibThe serum concentration of Ramelteon can be decreased when it is combined with Dabrafenib.Approved
DantroleneThe risk or severity of adverse effects can be increased when Ramelteon is combined with Dantrolene.Approved
DapiprazoleThe risk or severity of adverse effects can be increased when Dapiprazole is combined with Ramelteon.Approved
DapoxetineThe risk or severity of adverse effects can be increased when Ramelteon is combined with Dapoxetine.Investigational
DarunavirThe serum concentration of Ramelteon can be increased when it is combined with Darunavir.Approved
DasatinibThe serum concentration of Ramelteon can be increased when it is combined with Dasatinib.Approved, Investigational
DeferasiroxThe serum concentration of Ramelteon can be decreased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe serum concentration of Ramelteon can be increased when it is combined with Delavirdine.Approved
deramciclaneThe risk or severity of adverse effects can be increased when deramciclane is combined with Ramelteon.Investigational
DesfluraneThe risk or severity of adverse effects can be increased when Desflurane is combined with Ramelteon.Approved
DesipramineThe risk or severity of adverse effects can be increased when Ramelteon is combined with Desipramine.Approved
DesloratadineThe risk or severity of adverse effects can be increased when Desloratadine is combined with Ramelteon.Approved, Investigational
DesvenlafaxineThe risk or severity of adverse effects can be increased when Ramelteon is combined with Desvenlafaxine.Approved
DetomidineThe risk or severity of adverse effects can be increased when Detomidine is combined with Ramelteon.Vet Approved
DexamethasoneThe serum concentration of Ramelteon can be decreased when it is combined with Dexamethasone.Approved, Investigational, Vet Approved
DexbrompheniramineThe risk or severity of adverse effects can be increased when Dexbrompheniramine is combined with Ramelteon.Approved
DexmedetomidineThe risk or severity of adverse effects can be increased when Dexmedetomidine is combined with Ramelteon.Approved, Vet Approved
DextromoramideThe risk or severity of adverse effects can be increased when Dextromoramide is combined with Ramelteon.Experimental, Illicit
DextropropoxypheneThe risk or severity of adverse effects can be increased when Dextropropoxyphene is combined with Ramelteon.Approved, Illicit, Withdrawn
DezocineThe risk or severity of adverse effects can be increased when Dezocine is combined with Ramelteon.Approved
DiazepamThe risk or severity of adverse effects can be increased when Diazepam is combined with Ramelteon.Approved, Illicit, Vet Approved
DifenoxinThe risk or severity of adverse effects can be increased when Ramelteon is combined with Difenoxin.Approved, Illicit
DihydrocodeineThe risk or severity of adverse effects can be increased when Dihydrocodeine is combined with Ramelteon.Approved, Illicit
DihydroergotamineThe metabolism of Ramelteon can be decreased when combined with Dihydroergotamine.Approved
DihydroetorphineThe risk or severity of adverse effects can be increased when Dihydroetorphine is combined with Ramelteon.Experimental, Illicit
DihydromorphineThe risk or severity of adverse effects can be increased when Dihydromorphine is combined with Ramelteon.Experimental, Illicit
DiltiazemThe metabolism of Ramelteon can be decreased when combined with Diltiazem.Approved
DimenhydrinateThe risk or severity of adverse effects can be increased when Ramelteon is combined with Dimenhydrinate.Approved
DiphenhydramineThe risk or severity of adverse effects can be increased when Diphenhydramine is combined with Ramelteon.Approved
DiphenoxylateThe risk or severity of adverse effects can be increased when Diphenoxylate is combined with Ramelteon.Approved, Illicit
DoramectinThe risk or severity of adverse effects can be increased when Doramectin is combined with Ramelteon.Vet Approved
DoxepinThe risk or severity of adverse effects can be increased when Ramelteon is combined with Doxepin.Approved
DoxycyclineThe metabolism of Ramelteon can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DoxylamineDoxylamine may increase the central nervous system depressant (CNS depressant) activities of Ramelteon.Approved, Vet Approved
DPDPEThe risk or severity of adverse effects can be increased when DPDPE is combined with Ramelteon.Investigational
DronabinolDronabinol may increase the central nervous system depressant (CNS depressant) activities of Ramelteon.Approved, Illicit
DronedaroneThe metabolism of Ramelteon can be decreased when combined with Dronedarone.Approved
DroperidolDroperidol may increase the central nervous system depressant (CNS depressant) activities of Ramelteon.Approved, Vet Approved
DrotebanolThe risk or severity of adverse effects can be increased when Drotebanol is combined with Ramelteon.Experimental, Illicit
DuloxetineThe risk or severity of adverse effects can be increased when Ramelteon is combined with Duloxetine.Approved
DyclonineThe risk or severity of adverse effects can be increased when Dyclonine is combined with Ramelteon.Approved
EcgonineThe risk or severity of adverse effects can be increased when Ecgonine is combined with Ramelteon.Experimental, Illicit
ECGONINE METHYL ESTERThe risk or severity of adverse effects can be increased when ECGONINE METHYL ESTER is combined with Ramelteon.Experimental
EcopipamThe risk or severity of adverse effects can be increased when Ramelteon is combined with Ecopipam.Investigational
EfavirenzThe serum concentration of Ramelteon can be decreased when it is combined with Efavirenz.Approved, Investigational
EnfluraneThe risk or severity of adverse effects can be increased when Enflurane is combined with Ramelteon.Approved, Vet Approved
EntacaponeThe risk or severity of adverse effects can be increased when Entacapone is combined with Ramelteon.Approved, Investigational
EnzalutamideThe serum concentration of Ramelteon can be decreased when it is combined with Enzalutamide.Approved
ErythromycinThe metabolism of Ramelteon can be decreased when combined with Erythromycin.Approved, Vet Approved
EscitalopramThe risk or severity of adverse effects can be increased when Ramelteon is combined with Escitalopram.Approved, Investigational
Eslicarbazepine acetateThe serum concentration of Ramelteon can be decreased when it is combined with Eslicarbazepine acetate.Approved
EsomeprazoleThe metabolism of Ramelteon can be decreased when combined with Esomeprazole.Approved, Investigational
EstazolamThe risk or severity of adverse effects can be increased when Estazolam is combined with Ramelteon.Approved, Illicit
EszopicloneThe risk or severity of adverse effects can be increased when Eszopiclone is combined with Ramelteon.Approved
EthanolRamelteon may increase the central nervous system depressant (CNS depressant) activities of Ethanol.Approved
EthchlorvynolThe risk or severity of adverse effects can be increased when Ethchlorvynol is combined with Ramelteon.Approved, Illicit, Withdrawn
EthosuximideThe risk or severity of adverse effects can be increased when Ethosuximide is combined with Ramelteon.Approved
EthotoinThe risk or severity of adverse effects can be increased when Ethotoin is combined with Ramelteon.Approved
Ethyl carbamateThe risk or severity of adverse effects can be increased when Ethyl carbamate is combined with Ramelteon.Withdrawn
Ethyl loflazepateThe risk or severity of adverse effects can be increased when Ethyl loflazepate is combined with Ramelteon.Approved, Illicit
EthylmorphineThe risk or severity of adverse effects can be increased when Ethylmorphine is combined with Ramelteon.Approved, Illicit
EtidocaineThe risk or severity of adverse effects can be increased when Etidocaine is combined with Ramelteon.Approved
EtifoxineThe risk or severity of adverse effects can be increased when Etifoxine is combined with Ramelteon.Withdrawn
EtizolamThe risk or severity of adverse effects can be increased when Etizolam is combined with Ramelteon.Approved
EtomidateThe risk or severity of adverse effects can be increased when Etomidate is combined with Ramelteon.Approved
EtoperidoneThe risk or severity of adverse effects can be increased when Ramelteon is combined with Etoperidone.Approved
EtorphineThe risk or severity of adverse effects can be increased when Etorphine is combined with Ramelteon.Illicit, Vet Approved
EtravirineThe serum concentration of Ramelteon can be decreased when it is combined with Etravirine.Approved
EzogabineThe risk or severity of adverse effects can be increased when Ramelteon is combined with Ezogabine.Approved
FelbamateThe risk or severity of adverse effects can be increased when Felbamate is combined with Ramelteon.Approved
FencamfamineThe risk or severity of adverse effects can be increased when Fencamfamine is combined with Ramelteon.Approved, Illicit, Withdrawn
FentanylThe risk or severity of adverse effects can be increased when Fentanyl is combined with Ramelteon.Approved, Illicit, Investigational, Vet Approved
FexofenadineThe risk or severity of adverse effects can be increased when Fexofenadine is combined with Ramelteon.Approved
FlibanserinThe risk or severity of adverse effects can be increased when Ramelteon is combined with Flibanserin.Approved
FloxuridineThe serum concentration of Ramelteon can be increased when it is combined with Floxuridine.Approved
FluconazoleThe serum concentration of Ramelteon can be increased when it is combined with Fluconazole.Approved
FludiazepamThe risk or severity of adverse effects can be increased when Fludiazepam is combined with Ramelteon.Approved, Illicit
FlumazenilFlumazenil may decrease the sedative activities of Ramelteon.Approved
FlunarizineThe risk or severity of adverse effects can be increased when Ramelteon is combined with Flunarizine.Approved
FlunitrazepamThe risk or severity of adverse effects can be increased when Flunitrazepam is combined with Ramelteon.Approved, Illicit
FluorouracilThe serum concentration of Ramelteon can be increased when it is combined with Fluorouracil.Approved
FluoxetineThe metabolism of Ramelteon can be decreased when combined with Fluoxetine.Approved, Vet Approved
FlupentixolThe risk or severity of adverse effects can be increased when Flupentixol is combined with Ramelteon.Approved, Withdrawn
FluphenazineThe risk or severity of adverse effects can be increased when Fluphenazine is combined with Ramelteon.Approved
FlurazepamThe risk or severity of adverse effects can be increased when Flurazepam is combined with Ramelteon.Approved, Illicit
FluspirileneThe risk or severity of adverse effects can be increased when Fluspirilene is combined with Ramelteon.Approved
Fluticasone PropionateThe risk or severity of adverse effects can be increased when Fluticasone Propionate is combined with Ramelteon.Approved
FluvoxamineThe serum concentration of Ramelteon can be increased when it is combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe metabolism of Ramelteon can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Ramelteon can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe metabolism of Ramelteon can be increased when combined with Fosphenytoin.Approved
FospropofolThe risk or severity of adverse effects can be increased when Fospropofol is combined with Ramelteon.Approved, Illicit
Fusidic AcidThe serum concentration of Ramelteon can be increased when it is combined with Fusidic Acid.Approved
GabapentinThe risk or severity of adverse effects can be increased when Gabapentin is combined with Ramelteon.Approved, Investigational
gabapentin enacarbilThe risk or severity of adverse effects can be increased when Ramelteon is combined with gabapentin enacarbil.Approved
Gamma Hydroxybutyric AcidThe risk or severity of adverse effects can be increased when Gamma Hydroxybutyric Acid is combined with Ramelteon.Approved, Illicit
GemfibrozilThe serum concentration of Ramelteon can be increased when it is combined with Gemfibrozil.Approved
GepironeThe risk or severity of adverse effects can be increased when Ramelteon is combined with Gepirone.Investigational
GlutethimideThe risk or severity of adverse effects can be increased when Glutethimide is combined with Ramelteon.Approved, Illicit
GuanfacineThe risk or severity of adverse effects can be increased when Ramelteon is combined with Guanfacine.Approved, Investigational
HalazepamThe risk or severity of adverse effects can be increased when Halazepam is combined with Ramelteon.Approved, Illicit, Withdrawn
HaloperidolThe risk or severity of adverse effects can be increased when Haloperidol is combined with Ramelteon.Approved
HalothaneThe risk or severity of adverse effects can be increased when Halothane is combined with Ramelteon.Approved, Vet Approved
HeroinThe risk or severity of adverse effects can be increased when Heroin is combined with Ramelteon.Approved, Illicit
HexobarbitalThe risk or severity of adverse effects can be increased when Hexobarbital is combined with Ramelteon.Approved
HydrocodoneRamelteon may increase the central nervous system depressant (CNS depressant) activities of Hydrocodone.Approved, Illicit
HydromorphoneThe risk or severity of adverse effects can be increased when Hydromorphone is combined with Ramelteon.Approved, Illicit
HydroxyzineHydroxyzine may increase the central nervous system depressant (CNS depressant) activities of Ramelteon.Approved
IdelalisibThe serum concentration of Ramelteon can be increased when it is combined with Idelalisib.Approved
IloperidoneThe risk or severity of adverse effects can be increased when Ramelteon is combined with Iloperidone.Approved
ImatinibThe metabolism of Ramelteon can be decreased when combined with Imatinib.Approved
ImipramineThe risk or severity of adverse effects can be increased when Imipramine is combined with Ramelteon.Approved
IndalpineThe risk or severity of adverse effects can be increased when Ramelteon is combined with Indalpine.Investigational, Withdrawn
IndinavirThe serum concentration of Ramelteon can be increased when it is combined with Indinavir.Approved
IsavuconazoniumThe metabolism of Ramelteon can be decreased when combined with Isavuconazonium.Approved, Investigational
IsofluraneThe risk or severity of adverse effects can be increased when Isoflurane is combined with Ramelteon.Approved, Vet Approved
IsoniazidThe metabolism of Ramelteon can be decreased when combined with Isoniazid.Approved
IsradipineThe metabolism of Ramelteon can be decreased when combined with Isradipine.Approved
ItraconazoleThe serum concentration of Ramelteon can be increased when it is combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Ramelteon can be increased when it is combined with Ivacaftor.Approved
KetamineThe risk or severity of adverse effects can be increased when Ketamine is combined with Ramelteon.Approved, Vet Approved
KetazolamThe risk or severity of adverse effects can be increased when Ketazolam is combined with Ramelteon.Approved
KetobemidoneThe risk or severity of adverse effects can be increased when Ketobemidone is combined with Ramelteon.Approved
KetoconazoleThe serum concentration of Ramelteon can be increased when it is combined with Ketoconazole.Approved, Investigational
LamotrigineThe risk or severity of adverse effects can be increased when Lamotrigine is combined with Ramelteon.Approved, Investigational
LevetiracetamThe risk or severity of adverse effects can be increased when Ramelteon is combined with Levetiracetam.Approved, Investigational
LevobupivacaineThe risk or severity of adverse effects can be increased when Levobupivacaine is combined with Ramelteon.Approved
LevocabastineThe risk or severity of adverse effects can be increased when Ramelteon is combined with Levocabastine.Approved
LevocetirizineThe risk or severity of adverse effects can be increased when Ramelteon is combined with Levocetirizine.Approved
LevodopaThe risk or severity of adverse effects can be increased when Ramelteon is combined with Levodopa.Approved
Levomethadyl AcetateThe risk or severity of adverse effects can be increased when Levomethadyl Acetate is combined with Ramelteon.Approved
LevomilnacipranThe risk or severity of adverse effects can be increased when Ramelteon is combined with Levomilnacipran.Approved
LevorphanolThe risk or severity of adverse effects can be increased when Levorphanol is combined with Ramelteon.Approved
LidocaineThe metabolism of Ramelteon can be decreased when combined with Lidocaine.Approved, Vet Approved
LithiumThe risk or severity of adverse effects can be increased when Lithium is combined with Ramelteon.Approved
LofentanilThe risk or severity of adverse effects can be increased when Lofentanil is combined with Ramelteon.Illicit
LopinavirThe serum concentration of Ramelteon can be increased when it is combined with Lopinavir.Approved
LoratadineThe risk or severity of adverse effects can be increased when Loratadine is combined with Ramelteon.Approved
LorazepamThe risk or severity of adverse effects can be increased when Lorazepam is combined with Ramelteon.Approved
LovastatinThe metabolism of Ramelteon can be decreased when combined with Lovastatin.Approved, Investigational
LoxapineThe risk or severity of adverse effects can be increased when Loxapine is combined with Ramelteon.Approved
Lu AA21004The risk or severity of adverse effects can be increased when Lu AA21004 is combined with Ramelteon.Investigational
LuliconazoleThe serum concentration of Ramelteon can be increased when it is combined with Luliconazole.Approved
LumacaftorThe serum concentration of Ramelteon can be decreased when it is combined with Lumacaftor.Approved
LurasidoneThe risk or severity of adverse effects can be increased when Lurasidone is combined with Ramelteon.Approved
Magnesium SulfateMagnesium Sulfate may increase the central nervous system depressant (CNS depressant) activities of Ramelteon.Approved, Vet Approved
MaprotilineThe risk or severity of adverse effects can be increased when Maprotiline is combined with Ramelteon.Approved
MeclizineThe risk or severity of adverse effects can be increased when Meclizine is combined with Ramelteon.Approved
MedetomidineThe risk or severity of adverse effects can be increased when Medetomidine is combined with Ramelteon.Vet Approved
MelatoninThe risk or severity of adverse effects can be increased when Melatonin is combined with Ramelteon.Approved, Nutraceutical, Vet Approved
MelperoneThe risk or severity of adverse effects can be increased when Melperone is combined with Ramelteon.Approved
MepivacaineThe risk or severity of adverse effects can be increased when Mepivacaine is combined with Ramelteon.Approved, Vet Approved
MeprobamateThe risk or severity of adverse effects can be increased when Meprobamate is combined with Ramelteon.Approved, Illicit
MesoridazineThe risk or severity of adverse effects can be increased when Mesoridazine is combined with Ramelteon.Approved
MetaxaloneThe risk or severity of adverse effects can be increased when Metaxalone is combined with Ramelteon.Approved
MethadoneThe risk or severity of adverse effects can be increased when Methadone is combined with Ramelteon.Approved
Methadyl AcetateThe risk or severity of adverse effects can be increased when Methadyl Acetate is combined with Ramelteon.Approved, Illicit
MethapyrileneThe risk or severity of adverse effects can be increased when Methapyrilene is combined with Ramelteon.Withdrawn
MethaqualoneThe risk or severity of adverse effects can be increased when Methaqualone is combined with Ramelteon.Illicit, Withdrawn
MethocarbamolThe risk or severity of adverse effects can be increased when Methocarbamol is combined with Ramelteon.Approved, Vet Approved
MethohexitalThe risk or severity of adverse effects can be increased when Methohexital is combined with Ramelteon.Approved
MethotrimeprazineRamelteon may increase the central nervous system depressant (CNS depressant) activities of Methotrimeprazine.Approved
MethoxyfluraneThe risk or severity of adverse effects can be increased when Methoxyflurane is combined with Ramelteon.Approved, Vet Approved
MethsuximideThe risk or severity of adverse effects can be increased when Ramelteon is combined with Methsuximide.Approved
MethylphenobarbitalThe risk or severity of adverse effects can be increased when Methylphenobarbital is combined with Ramelteon.Approved
MetyrosineRamelteon may increase the sedative activities of Metyrosine.Approved
MexiletineThe metabolism of Ramelteon can be decreased when combined with Mexiletine.Approved
MidazolamThe risk or severity of adverse effects can be increased when Midazolam is combined with Ramelteon.Approved, Illicit
MifepristoneThe serum concentration of Ramelteon can be increased when it is combined with Mifepristone.Approved, Investigational
MilnacipranThe risk or severity of adverse effects can be increased when Ramelteon is combined with Milnacipran.Approved
MinocyclineMinocycline may increase the central nervous system depressant (CNS depressant) activities of Ramelteon.Approved, Investigational
MirtazapineRamelteon may increase the central nervous system depressant (CNS depressant) activities of Mirtazapine.Approved
MitotaneThe serum concentration of Ramelteon can be decreased when it is combined with Mitotane.Approved
MoclobemideThe metabolism of Ramelteon can be decreased when combined with Moclobemide.Approved
ModafinilThe serum concentration of Ramelteon can be decreased when it is combined with Modafinil.Approved, Investigational
MolindoneThe risk or severity of adverse effects can be increased when Molindone is combined with Ramelteon.Approved
MorphineThe risk or severity of adverse effects can be increased when Morphine is combined with Ramelteon.Approved, Investigational
NabiloneNabilone may increase the central nervous system depressant (CNS depressant) activities of Ramelteon.Approved, Investigational
NafcillinThe serum concentration of Ramelteon can be decreased when it is combined with Nafcillin.Approved
NalbuphineThe risk or severity of adverse effects can be increased when Nalbuphine is combined with Ramelteon.Approved
NefazodoneThe serum concentration of Ramelteon can be increased when it is combined with Nefazodone.Approved, Withdrawn
NelfinavirThe serum concentration of Ramelteon can be increased when it is combined with Nelfinavir.Approved
NetupitantThe serum concentration of Ramelteon can be increased when it is combined with Netupitant.Approved
NevirapineThe metabolism of Ramelteon can be increased when combined with Nevirapine.Approved
NicardipineThe serum concentration of Ramelteon can be increased when it is combined with Nicardipine.Approved
NilotinibThe metabolism of Ramelteon can be decreased when combined with Nilotinib.Approved, Investigational
NitrazepamThe risk or severity of adverse effects can be increased when Nitrazepam is combined with Ramelteon.Approved
Nitrous oxideThe risk or severity of adverse effects can be increased when Nitrous oxide is combined with Ramelteon.Approved, Vet Approved
NormethadoneThe risk or severity of adverse effects can be increased when Normethadone is combined with Ramelteon.Approved, Illicit
NortriptylineThe risk or severity of adverse effects can be increased when Nortriptyline is combined with Ramelteon.Approved
OlanzapineThe risk or severity of adverse effects can be increased when Olanzapine is combined with Ramelteon.Approved, Investigational
OlaparibThe metabolism of Ramelteon can be decreased when combined with Olaparib.Approved
OlopatadineThe risk or severity of adverse effects can be increased when Olopatadine is combined with Ramelteon.Approved
OmeprazoleThe metabolism of Ramelteon can be decreased when combined with Omeprazole.Approved, Investigational, Vet Approved
OndansetronThe risk or severity of adverse effects can be increased when Ondansetron is combined with Ramelteon.Approved
OpiumThe risk or severity of adverse effects can be increased when Opium is combined with Ramelteon.Approved, Illicit
OrphenadrineRamelteon may increase the central nervous system depressant (CNS depressant) activities of Orphenadrine.Approved
OsanetantThe risk or severity of adverse effects can be increased when Osanetant is combined with Ramelteon.Investigational
OsimertinibThe serum concentration of Ramelteon can be increased when it is combined with Osimertinib.Approved
OxazepamThe risk or severity of adverse effects can be increased when Oxazepam is combined with Ramelteon.Approved
OxetacaineThe risk or severity of adverse effects can be increased when Ramelteon is combined with Oxetacaine.Investigational
OxprenololThe risk or severity of adverse effects can be increased when Oxprenolol is combined with Ramelteon.Approved
OxybuprocaineThe risk or severity of adverse effects can be increased when Oxybuprocaine is combined with Ramelteon.Approved
OxycodoneThe risk or severity of adverse effects can be increased when Oxycodone is combined with Ramelteon.Approved, Illicit, Investigational
OxymorphoneThe risk or severity of adverse effects can be increased when Oxymorphone is combined with Ramelteon.Approved, Investigational, Vet Approved
PalbociclibThe serum concentration of Ramelteon can be increased when it is combined with Palbociclib.Approved
PaliperidoneThe risk or severity of adverse effects can be increased when Paliperidone is combined with Ramelteon.Approved
PantoprazoleThe metabolism of Ramelteon can be decreased when combined with Pantoprazole.Approved
ParaldehydeRamelteon may increase the central nervous system depressant (CNS depressant) activities of Paraldehyde.Approved
ParoxetineThe risk or severity of adverse effects can be increased when Ramelteon is combined with Paroxetine.Approved, Investigational
Peginterferon alfa-2bThe serum concentration of Ramelteon can be increased when it is combined with Peginterferon alfa-2b.Approved
PentazocineThe risk or severity of adverse effects can be increased when Pentazocine is combined with Ramelteon.Approved, Vet Approved
PentobarbitalThe metabolism of Ramelteon can be increased when combined with Pentobarbital.Approved, Vet Approved
PerampanelPerampanel may increase the central nervous system depressant (CNS depressant) activities of Ramelteon.Approved
PerazineThe risk or severity of adverse effects can be increased when Ramelteon is combined with Perazine.Investigational
PerospironeThe risk or severity of adverse effects can be increased when Perospirone is combined with Ramelteon.Approved
PerphenazineThe risk or severity of adverse effects can be increased when Perphenazine is combined with Ramelteon.Approved
PethidineThe risk or severity of adverse effects can be increased when Pethidine is combined with Ramelteon.Approved
PhenobarbitalThe metabolism of Ramelteon can be increased when combined with Phenobarbital.Approved
PhenoxyethanolThe risk or severity of adverse effects can be increased when Phenoxyethanol is combined with Ramelteon.Approved
PhenytoinThe metabolism of Ramelteon can be increased when combined with Phenytoin.Approved, Vet Approved
PimozideThe risk or severity of adverse effects can be increased when Pimozide is combined with Ramelteon.Approved
PipamperoneThe risk or severity of adverse effects can be increased when Pipamperone is combined with Ramelteon.Approved
PipotiazineThe risk or severity of adverse effects can be increased when Ramelteon is combined with Pipotiazine.Approved
PiritramideThe risk or severity of adverse effects can be increased when Ramelteon is combined with Piritramide.Investigational
PizotifenThe risk or severity of adverse effects can be increased when Ramelteon is combined with Pizotifen.Approved
PomalidomideThe risk or severity of adverse effects can be increased when Ramelteon is combined with Pomalidomide.Approved
PosaconazoleThe serum concentration of Ramelteon can be increased when it is combined with Posaconazole.Approved, Investigational, Vet Approved
PramipexoleRamelteon may increase the sedative activities of Pramipexole.Approved, Investigational
PramocaineThe risk or severity of adverse effects can be increased when Pramocaine is combined with Ramelteon.Approved
PrazepamThe risk or severity of adverse effects can be increased when Prazepam is combined with Ramelteon.Approved, Illicit
PregabalinThe risk or severity of adverse effects can be increased when Pregabalin is combined with Ramelteon.Approved, Illicit, Investigational
PregnanoloneThe risk or severity of adverse effects can be increased when Ramelteon is combined with Pregnanolone.Investigational
PrilocaineThe risk or severity of adverse effects can be increased when Prilocaine is combined with Ramelteon.Approved
PrimidoneThe metabolism of Ramelteon can be increased when combined with Primidone.Approved, Vet Approved
ProcaineThe risk or severity of adverse effects can be increased when Procaine is combined with Ramelteon.Approved, Investigational, Vet Approved
ProchlorperazineThe risk or severity of adverse effects can be increased when Prochlorperazine is combined with Ramelteon.Approved, Vet Approved
PromazineThe risk or severity of adverse effects can be increased when Promazine is combined with Ramelteon.Approved, Vet Approved
PromethazineThe risk or severity of adverse effects can be increased when Ramelteon is combined with Promethazine.Approved
ProparacaineThe risk or severity of adverse effects can be increased when Proparacaine is combined with Ramelteon.Approved, Vet Approved
PropofolThe risk or severity of adverse effects can be increased when Propofol is combined with Ramelteon.Approved, Investigational, Vet Approved
PropoxycaineThe risk or severity of adverse effects can be increased when Propoxycaine is combined with Ramelteon.Approved
ProtriptylineThe risk or severity of adverse effects can be increased when Protriptyline is combined with Ramelteon.Approved
PSD502The risk or severity of adverse effects can be increased when PSD502 is combined with Ramelteon.Investigational
QuazepamThe risk or severity of adverse effects can be increased when Quazepam is combined with Ramelteon.Approved, Illicit
QuetiapineThe risk or severity of adverse effects can be increased when Quetiapine is combined with Ramelteon.Approved
RacloprideThe risk or severity of adverse effects can be increased when Ramelteon is combined with Raclopride.Investigational
RanolazineThe metabolism of Ramelteon can be decreased when combined with Ranolazine.Approved, Investigational
RemifentanilThe risk or severity of adverse effects can be increased when Remifentanil is combined with Ramelteon.Approved
RemoxiprideThe risk or severity of adverse effects can be increased when Remoxipride is combined with Ramelteon.Approved, Withdrawn
ReserpineThe risk or severity of adverse effects can be increased when Reserpine is combined with Ramelteon.Approved
RifabutinThe metabolism of Ramelteon can be increased when combined with Rifabutin.Approved
RifampicinThe metabolism of Ramelteon can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of Ramelteon can be increased when combined with Rifapentine.Approved
RisperidoneThe risk or severity of adverse effects can be increased when Risperidone is combined with Ramelteon.Approved, Investigational
RitanserinThe risk or severity of adverse effects can be increased when Ramelteon is combined with Ritanserin.Investigational
RitonavirThe serum concentration of Ramelteon can be increased when it is combined with Ritonavir.Approved, Investigational
RomifidineThe risk or severity of adverse effects can be increased when Romifidine is combined with Ramelteon.Vet Approved
RopiniroleRamelteon may increase the sedative activities of Ropinirole.Approved, Investigational
RopivacaineThe risk or severity of adverse effects can be increased when Ropivacaine is combined with Ramelteon.Approved
RotigotineRamelteon may increase the sedative activities of Rotigotine.Approved
RufinamideThe risk or severity of adverse effects can be increased when Rufinamide is combined with Ramelteon.Approved
S-EthylisothioureaThe risk or severity of adverse effects can be increased when S-Ethylisothiourea is combined with Ramelteon.Experimental
Sage 547The risk or severity of adverse effects can be increased when Ramelteon is combined with Sage 547.Investigational
SaquinavirThe serum concentration of Ramelteon can be increased when it is combined with Saquinavir.Approved, Investigational
ScopolamineThe risk or severity of adverse effects can be increased when Scopolamine is combined with Ramelteon.Approved
SecobarbitalThe risk or severity of adverse effects can be increased when Secobarbital is combined with Ramelteon.Approved, Vet Approved
SertindoleThe risk or severity of adverse effects can be increased when Sertindole is combined with Ramelteon.Approved, Withdrawn
SertralineThe metabolism of Ramelteon can be decreased when combined with Sertraline.Approved
SevofluraneThe risk or severity of adverse effects can be increased when Sevoflurane is combined with Ramelteon.Approved, Vet Approved
SildenafilThe metabolism of Ramelteon can be decreased when combined with Sildenafil.Approved, Investigational
SiltuximabThe serum concentration of Ramelteon can be decreased when it is combined with Siltuximab.Approved
SimeprevirThe serum concentration of Ramelteon can be increased when it is combined with Simeprevir.Approved
Sodium oxybateRamelteon may increase the central nervous system depressant (CNS depressant) activities of Sodium oxybate.Approved
St. John's WortThe serum concentration of Ramelteon can be decreased when it is combined with St. John's Wort.Nutraceutical
StiripentolThe serum concentration of Ramelteon can be increased when it is combined with Stiripentol.Approved
SufentanilThe risk or severity of adverse effects can be increased when Sufentanil is combined with Ramelteon.Approved, Investigational
SulfadiazineThe serum concentration of Ramelteon can be increased when it is combined with Sulfadiazine.Approved, Vet Approved
SulfisoxazoleThe serum concentration of Ramelteon can be increased when it is combined with Sulfisoxazole.Approved, Vet Approved
SulpirideThe risk or severity of adverse effects can be increased when Sulpiride is combined with Ramelteon.Approved
SuvorexantRamelteon may increase the central nervous system depressant (CNS depressant) activities of Suvorexant.Approved
TandospironeThe risk or severity of adverse effects can be increased when Ramelteon is combined with Tandospirone.Investigational
TapentadolTapentadol may increase the central nervous system depressant (CNS depressant) activities of Ramelteon.Approved
TasimelteonThe risk or severity of adverse effects can be increased when Ramelteon is combined with Tasimelteon.Approved
TelaprevirThe serum concentration of Ramelteon can be increased when it is combined with Telaprevir.Approved
TelithromycinThe serum concentration of Ramelteon can be increased when it is combined with Telithromycin.Approved
TemazepamThe risk or severity of adverse effects can be increased when Temazepam is combined with Ramelteon.Approved
TenofovirThe metabolism of Ramelteon can be decreased when combined with Tenofovir.Approved, Investigational
TeriflunomideThe serum concentration of Ramelteon can be decreased when it is combined with Teriflunomide.Approved
TetrabenazineThe risk or severity of adverse effects can be increased when Ramelteon is combined with Tetrabenazine.Approved
TetracaineThe risk or severity of adverse effects can be increased when Tetracaine is combined with Ramelteon.Approved, Vet Approved
TetrodotoxinThe risk or severity of adverse effects can be increased when Tetrodotoxin is combined with Ramelteon.Investigational
ThalidomideRamelteon may increase the central nervous system depressant (CNS depressant) activities of Thalidomide.Approved, Investigational, Withdrawn
TheophyllineThe metabolism of Ramelteon can be decreased when combined with Theophylline.Approved
ThiamylalThe risk or severity of adverse effects can be increased when Thiamylal is combined with Ramelteon.Approved, Vet Approved
ThiopentalThe risk or severity of adverse effects can be increased when Thiopental is combined with Ramelteon.Approved, Vet Approved
ThioridazineThe risk or severity of adverse effects can be increased when Thioridazine is combined with Ramelteon.Approved
ThiothixeneThe risk or severity of adverse effects can be increased when Thiothixene is combined with Ramelteon.Approved
TiagabineThe risk or severity of adverse effects can be increased when Tiagabine is combined with Ramelteon.Approved
TiaprideThe risk or severity of adverse effects can be increased when Ramelteon is combined with Tiapride.Investigational
TiclopidineThe metabolism of Ramelteon can be decreased when combined with Ticlopidine.Approved
TiletamineThe risk or severity of adverse effects can be increased when Tiletamine is combined with Ramelteon.Vet Approved
TizanidineThe risk or severity of adverse effects can be increased when Tizanidine is combined with Ramelteon.Approved
TocilizumabThe serum concentration of Ramelteon can be decreased when it is combined with Tocilizumab.Approved
TolbutamideThe serum concentration of Ramelteon can be increased when it is combined with Tolbutamide.Approved
TolcaponeThe risk or severity of adverse effects can be increased when Tolcapone is combined with Ramelteon.Approved, Withdrawn
TopiramateThe risk or severity of adverse effects can be increased when Topiramate is combined with Ramelteon.Approved
TramadolThe risk or severity of adverse effects can be increased when Tramadol is combined with Ramelteon.Approved, Investigational
Trans-2-PhenylcyclopropylamineThe risk or severity of adverse effects can be increased when Trans-2-Phenylcyclopropylamine is combined with Ramelteon.Experimental
TranylcypromineThe risk or severity of adverse effects can be increased when Tranylcypromine is combined with Ramelteon.Approved
TrazodoneThe risk or severity of adverse effects can be increased when Trazodone is combined with Ramelteon.Approved, Investigational
TriazolamThe risk or severity of adverse effects can be increased when Triazolam is combined with Ramelteon.Approved
TrifluoperazineThe risk or severity of adverse effects can be increased when Trifluoperazine is combined with Ramelteon.Approved
TriflupromazineThe risk or severity of adverse effects can be increased when Triflupromazine is combined with Ramelteon.Approved, Vet Approved
TrimipramineThe risk or severity of adverse effects can be increased when Trimipramine is combined with Ramelteon.Approved
TriprolidineThe risk or severity of adverse effects can be increased when Triprolidine is combined with Ramelteon.Approved
Uc1010The risk or severity of adverse effects can be increased when Ramelteon is combined with Uc1010.Investigational
Valproic AcidThe risk or severity of adverse effects can be increased when Valproic Acid is combined with Ramelteon.Approved, Investigational
VemurafenibThe serum concentration of Ramelteon can be increased when it is combined with Vemurafenib.Approved
VenlafaxineThe metabolism of Ramelteon can be decreased when combined with Venlafaxine.Approved
VerapamilThe metabolism of Ramelteon can be decreased when combined with Verapamil.Approved
VigabatrinThe risk or severity of adverse effects can be increased when Ramelteon is combined with Vigabatrin.Approved
VoriconazoleThe serum concentration of Ramelteon can be increased when it is combined with Voriconazole.Approved, Investigational
VortioxetineThe risk or severity of adverse effects can be increased when Vortioxetine is combined with Ramelteon.Approved
XylazineThe risk or severity of adverse effects can be increased when Xylazine is combined with Ramelteon.Vet Approved
ZaleplonThe risk or severity of adverse effects can be increased when Zaleplon is combined with Ramelteon.Approved, Illicit, Investigational
ZiconotideThe risk or severity of adverse effects can be increased when Ramelteon is combined with Ziconotide.Approved
ZimelidineThe risk or severity of adverse effects can be increased when Ramelteon is combined with Zimelidine.Withdrawn
ZiprasidoneThe metabolism of Ramelteon can be decreased when combined with Ziprasidone.Approved
ZolazepamThe risk or severity of adverse effects can be increased when Zolazepam is combined with Ramelteon.Vet Approved
ZolpidemRamelteon may increase the central nervous system depressant (CNS depressant) activities of Zolpidem.Approved
ZonisamideThe risk or severity of adverse effects can be increased when Zonisamide is combined with Ramelteon.Approved, Investigational
ZopicloneThe risk or severity of adverse effects can be increased when Zopiclone is combined with Ramelteon.Approved
ZotepineThe risk or severity of adverse effects can be increased when Zotepine is combined with Ramelteon.Approved
ZuclopenthixolThe risk or severity of adverse effects can be increased when Zuclopenthixol is combined with Ramelteon.Approved, Investigational
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
ATC CodesN05CH02
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (2.36 MB)
MSDSNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9934
Caco-2 permeable+0.5893
P-glycoprotein substrateSubstrate0.5211
P-glycoprotein inhibitor INon-inhibitor0.8548
P-glycoprotein inhibitor IINon-inhibitor0.7877
Renal organic cation transporterNon-inhibitor0.6381
CYP450 2C9 substrateNon-substrate0.7876
CYP450 2D6 substrateNon-substrate0.6392
CYP450 3A4 substrateSubstrate0.512
CYP450 1A2 substrateInhibitor0.7314
CYP450 2C9 inhibitorNon-inhibitor0.6471
CYP450 2D6 inhibitorNon-inhibitor0.5916
CYP450 2C19 inhibitorInhibitor0.8314
CYP450 3A4 inhibitorNon-inhibitor0.9196
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7763
Ames testNon AMES toxic0.7016
CarcinogenicityNon-carcinogens0.8206
BiodegradationReady biodegradable0.6635
Rat acute toxicity2.1034 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7898
hERG inhibition (predictor II)Inhibitor0.5
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Takeda global research development center inc
Packagers
Dosage forms
FormRouteStrength
Tablet, film coatedOral8 mg/1
Prices
Unit descriptionCostUnit
Rozerem 8 mg tablet5.17USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6034239 No1999-07-222019-07-22Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
logP2.4Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0164 mg/mLALOGPS
logP3.03ALOGPS
logP2.57ChemAxon
logS-4.2ALOGPS
pKa (Strongest Acidic)15.82ChemAxon
pKa (Strongest Basic)-0.4ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area38.33 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity75.52 m3·mol-1ChemAxon
Polarizability29.99 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as benzofurans. These are organic compounds containing a benzene ring fused to a furan. Furan is a five-membered aromatic ring with four carbon atoms and one oxygen atom.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzofurans
Sub ClassNot Available
Direct ParentBenzofurans
Alternative Parents
Substituents
  • Indane
  • Benzofuran
  • Alkyl aryl ether
  • Benzenoid
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Oxacycle
  • Ether
  • Carboxylic acid derivative
  • Carboxylic acid amide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
multitarget
General Function:
Melatonin receptor activity
Specific Function:
High affinity receptor for melatonin. Likely to mediates the reproductive and circadian actions of melatonin. The activity of this receptor is mediated by pertussis toxin sensitive G proteins that inhibit adenylate cyclase activity.
Gene Name:
MTNR1B
Uniprot ID:
P49286
Molecular Weight:
40187.895 Da
References
  1. Kato K, Hirai K, Nishiyama K, Uchikawa O, Fukatsu K, Ohkawa S, Kawamata Y, Hinuma S, Miyamoto M: Neurochemical properties of ramelteon (TAK-375), a selective MT1/MT2 receptor agonist. Neuropharmacology. 2005 Feb;48(2):301-10. [PubMed:15695169 ]
  2. 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 ]
  3. Greenblatt DJ, Harmatz JS, Karim A: Age and gender effects on the pharmacokinetics and pharmacodynamics of ramelteon, a hypnotic agent acting via melatonin receptors MT1 and MT2. J Clin Pharmacol. 2007 Apr;47(4):485-96. [PubMed:17389558 ]
  4. 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 ]
  5. Miyamoto M: Effect of ramelteon (TAK-375), a selective MT1/MT2 receptor agonist, on motor performance in mice. Neurosci Lett. 2006 Jul 24;402(3):201-4. Epub 2006 May 24. [PubMed:16730121 ]
  6. Authors unspecified: Ramelteon: TAK 375. Drugs R D. 2005;6(3):186-8. [PubMed:15869323 ]
  7. 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 ]
  8. Miyamoto M: [A novel therapeutic drug: ramelteon]. Nihon Rinsho. 2009 Aug;67(8):1595-600. [PubMed:19768947 ]
  9. 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 ]
  10. Borja NL, Daniel KL: Ramelteon for the treatment of insomnia. Clin Ther. 2006 Oct;28(10):1540-55. [PubMed:17157111 ]
  11. Johnson MW, Suess PE, Griffiths RR: Ramelteon: a novel hypnotic lacking abuse liability and sedative adverse effects. Arch Gen Psychiatry. 2006 Oct;63(10):1149-57. [PubMed:17015817 ]
  12. Zammit G, Erman M, Wang-Weigand S, Sainati S, Zhang J, Roth T: Evaluation of the efficacy and safety of ramelteon in subjects with chronic insomnia. J Clin Sleep Med. 2007 Aug 15;3(5):495-504. [PubMed:17803013 ]
  13. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
multitarget
General Function:
Organic cyclic compound binding
Specific Function:
High affinity receptor for melatonin. Likely to mediates the reproductive and circadian actions of melatonin. The activity of this receptor is mediated by pertussis toxin sensitive G proteins that inhibit adenylate cyclase activity.
Gene Name:
MTNR1A
Uniprot ID:
P48039
Molecular Weight:
39374.315 Da
References
  1. Kato K, Hirai K, Nishiyama K, Uchikawa O, Fukatsu K, Ohkawa S, Kawamata Y, Hinuma S, Miyamoto M: Neurochemical properties of ramelteon (TAK-375), a selective MT1/MT2 receptor agonist. Neuropharmacology. 2005 Feb;48(2):301-10. [PubMed:15695169 ]
  2. 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 ]
  3. Greenblatt DJ, Harmatz JS, Karim A: Age and gender effects on the pharmacokinetics and pharmacodynamics of ramelteon, a hypnotic agent acting via melatonin receptors MT1 and MT2. J Clin Pharmacol. 2007 Apr;47(4):485-96. [PubMed:17389558 ]
  4. 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 ]
  5. Miyamoto M: Effect of ramelteon (TAK-375), a selective MT1/MT2 receptor agonist, on motor performance in mice. Neurosci Lett. 2006 Jul 24;402(3):201-4. Epub 2006 May 24. [PubMed:16730121 ]
  6. Authors unspecified: Ramelteon: TAK 375. Drugs R D. 2005;6(3):186-8. [PubMed:15869323 ]
  7. 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 ]
  8. Miyamoto M: [A novel therapeutic drug: ramelteon]. Nihon Rinsho. 2009 Aug;67(8):1595-600. [PubMed:19768947 ]
  9. 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 ]
  10. Borja NL, Daniel KL: Ramelteon for the treatment of insomnia. Clin Ther. 2006 Oct;28(10):1540-55. [PubMed:17157111 ]
  11. Johnson MW, Suess PE, Griffiths RR: Ramelteon: a novel hypnotic lacking abuse liability and sedative adverse effects. Arch Gen Psychiatry. 2006 Oct;63(10):1149-57. [PubMed:17015817 ]
  12. Zammit G, Erman M, Wang-Weigand S, Sainati S, Zhang J, Roth T: Evaluation of the efficacy and safety of ramelteon in subjects with chronic insomnia. J Clin Sleep Med. 2007 Aug 15;3(5):495-504. [PubMed:17803013 ]
  13. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N...
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular Weight:
58293.76 Da
References
  1. Obach RS, Ryder TF: Metabolism of ramelteon in human liver microsomes and correlation with the effect of fluvoxamine on ramelteon pharmacokinetics. Drug Metab Dispos. 2010 Aug;38(8):1381-91. doi: 10.1124/dmd.110.034009. Epub 2010 May 17. [PubMed:20478852 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Steroid hydroxylase activity
Specific Function:
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.
Gene Name:
CYP2C19
Uniprot ID:
P33261
Molecular Weight:
55930.545 Da
References
  1. Obach RS, Ryder TF: Metabolism of ramelteon in human liver microsomes and correlation with the effect of fluvoxamine on ramelteon pharmacokinetics. Drug Metab Dispos. 2010 Aug;38(8):1381-91. doi: 10.1124/dmd.110.034009. Epub 2010 May 17. [PubMed:20478852 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
References
  1. Obach RS, Ryder TF: Metabolism of ramelteon in human liver microsomes and correlation with the effect of fluvoxamine on ramelteon pharmacokinetics. Drug Metab Dispos. 2010 Aug;38(8):1381-91. doi: 10.1124/dmd.110.034009. Epub 2010 May 17. [PubMed:20478852 ]
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Drug created on June 13, 2005 07:24 / Updated on December 03, 2016 02:45