ramelteon Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
2355 196597-26-9

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • ramelteon
  • rozerem
  • TAK-375
Ramelteon is a melatonin receptor agonist with both high affinity for melatonin MT1 and MT2 receptors and selectivity over the MT3 receptor. Ramelteon demonstrates full agonist activity in vitro in cells expressing human MT1 or MT2 receptors. The activity of ramelteon at the MT1 and MT2 receptors is believed to contribute to its sleep-promoting properties, as these receptors, acted upon by endogenous melatonin, are thought to be involved in the maintenance of the circadian rhythm underlying the normal sleep-wake cycle.
  • Molecular weight: 259.35
  • Formula: C16H21NO2
  • CLOGP: 2.48
  • LIPINSKI: 0
  • HAC: 3
  • HDO: 1
  • TPSA: 38.33
  • ALOGS: -4.20
  • ROTB: 4

  • Status: OFP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 0.10 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 0.44 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 1.80 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 1.05 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 13.10 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.20 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 1.90 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
July 22, 2005 FDA TAKEDA PHARMS USA

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Initial insomnia 130.13 17.07 38 4813 4414 46676797
Abnormal dreams 124.61 17.07 45 4806 10234 46670977
Nightmare 110.28 17.07 47 4804 16551 46664660
Middle insomnia 109.16 17.07 40 4811 9475 46671736
Product dispensing error 67.50 17.07 28 4823 9205 46672006
Somnolence 64.13 17.07 80 4771 156441 46524770
Poor quality sleep 62.85 17.07 31 4820 15222 46665989
Insomnia 57.73 17.07 78 4773 164846 46516365
Altered state of consciousness 35.79 17.07 25 4826 23323 46657888
Hallucination 35.18 17.07 34 4817 49917 46631294
Hepatic function abnormal 31.21 17.07 27 4824 34394 46646817
Ovarian cancer recurrent 31.17 17.07 9 4842 1002 46680209
Restlessness 29.38 17.07 23 4828 25501 46655710
Somnambulism 29.30 17.07 13 4838 5024 46676187
Intentional overdose 27.81 17.07 34 4817 64910 46616301
Galactorrhoea 26.01 17.07 11 4840 3786 46677425
Hangover 24.82 17.07 8 4843 1287 46679924
Feeling abnormal 24.00 17.07 45 4806 125015 46556196
Anxiety 22.77 17.07 55 4796 181902 46499309
Hypersomnia 22.43 17.07 16 4835 15423 46665788
Drug eruption 19.88 17.07 17 4834 21312 46659899
Impulsive behaviour 19.73 17.07 7 4844 1508 46679703
Product administered to patient of inappropriate age 19.10 17.07 8 4843 2688 46678523

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Somnolence 69.28 18.86 69 3331 96694 29852384
Initial insomnia 69.01 18.86 21 3379 2568 29946510
Middle insomnia 52.53 18.86 21 3379 5752 29943326
Hangover 52.51 18.86 14 3386 1064 29948014
Nightmare 51.97 18.86 26 3374 12050 29937028
Abnormal dreams 48.80 18.86 22 3378 8093 29940985
Pneumonia aspiration 42.91 18.86 35 3365 37745 29911333
Poor quality sleep 38.42 18.86 18 3382 7223 29941855
Interstitial lung disease 32.47 18.86 37 3363 60160 29888918
Delirium 30.88 18.86 30 3370 40601 29908477
Cerebral infarction 26.95 18.86 23 3377 26350 29922728
Disseminated intravascular coagulation 24.02 18.86 20 3380 22151 29926927
Restlessness 23.68 18.86 20 3380 22579 29926499
Hepatic function abnormal 21.28 18.86 25 3375 41920 29907158
Enterocolitis 19.18 18.86 11 3389 6676 29942402

Pharmacologic Action:

SourceCodeDescription
ATC N05CH02 NERVOUS SYSTEM
PSYCHOLEPTICS
HYPNOTICS AND SEDATIVES
Melatonin receptor agonists
FDA MoA N0000000250 Melatonin Receptor Agonists
FDA EPC N0000175743 Melatonin Receptor Agonist

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Initial insomnia indication 59050008
Suicidal thoughts contraindication 6471006
Alcoholism contraindication 7200002
Depressive disorder contraindication 35489007
Hepatic failure contraindication 59927004
Sleep apnea contraindication 73430006 DOID:0050847
Disease of liver contraindication 235856003 DOID:409
Hyperprolactinemia contraindication 237662005 DOID:12700
Sleep automatism contraindication 247962006

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 13.14 acidic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Melatonin receptor type 1B GPCR AGONIST Ki 10.39 WOMBAT-PK CHEMBL
Melatonin receptor type 1A GPCR AGONIST Ki 10.90 WOMBAT-PK CHEMBL

External reference:

IDSource
4024923 VUID
N0000171613 NUI
D02689 KEGG_DRUG
4024923 VANDF
C1565316 UMLSCUI
CHEBI:109549 CHEBI
JEV PDB_CHEM_ID
CHEMBL1218 ChEMBL_ID
DB00980 DRUGBANK_ID
1356 IUPHAR_LIGAND_ID
C495910 MESH_SUPPLEMENTAL_RECORD_UI
8447 INN_ID
901AS54I69 UNII
208902 PUBCHEM_CID
596205 RXNORM
20324 MMSL
320752 MMSL
70325 MMSL
d05578 MMSL
010947 NDDF
419588002 SNOMEDCT_US
419878007 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Ramelteon HUMAN PRESCRIPTION DRUG LABEL 1 0591-2191 TABLET 8 mg ORAL ANDA 27 sections
Ramelteon HUMAN PRESCRIPTION DRUG LABEL 1 0832-1250 TABLET, FILM COATED 8 mg ORAL ANDA 30 sections
Rozerem HUMAN PRESCRIPTION DRUG LABEL 1 21695-183 TABLET, FILM COATED 8 mg ORAL NDA 30 sections
Ramelteon HUMAN PRESCRIPTION DRUG LABEL 1 42291-776 TABLET 8 mg ORAL ANDA 26 sections
Ramelteon HUMAN PRESCRIPTION DRUG LABEL 1 43598-741 TABLET 8 mg ORAL ANDA 25 sections
Ramelteon HUMAN PRESCRIPTION DRUG LABEL 1 50268-708 TABLET 8 mg ORAL ANDA 26 sections
Ramelteon HUMAN PRESCRIPTION DRUG LABEL 1 51407-375 TABLET 8 mg ORAL ANDA 26 sections
Ramelteon HUMAN PRESCRIPTION DRUG LABEL 1 52817-235 TABLET, FILM COATED 8 mg ORAL ANDA 28 sections
Rozerem HUMAN PRESCRIPTION DRUG LABEL 1 54868-5649 TABLET, FILM COATED 8 mg ORAL NDA 18 sections
Ramelteon HUMAN PRESCRIPTION DRUG LABEL 1 55700-874 TABLET, FILM COATED 8 mg ORAL ANDA 28 sections
Ramelteon HUMAN PRESCRIPTION DRUG LABEL 1 63629-8264 TABLET 8 mg ORAL ANDA 28 sections
Ramelteon HUMAN PRESCRIPTION DRUG LABEL 1 63629-8531 TABLET 8 mg ORAL ANDA 26 sections
Rozerem HUMAN PRESCRIPTION DRUG LABEL 1 64764-805 TABLET, FILM COATED 8 mg ORAL NDA 27 sections
Rozerem HUMAN PRESCRIPTION DRUG LABEL 1 68151-4881 TABLET, FILM COATED 8 mg ORAL NDA 28 sections
Ramelteon HUMAN PRESCRIPTION DRUG LABEL 1 70010-028 TABLET 8 mg ORAL ANDA 26 sections
Ramelteon HUMAN PRESCRIPTION DRUG LABEL 1 70710-1344 TABLET 8 mg ORAL ANDA 27 sections
Ramelteon HUMAN PRESCRIPTION DRUG LABEL 1 70771-1495 TABLET 8 mg ORAL ANDA 1 sections
RAMELTEON HUMAN PRESCRIPTION DRUG LABEL 1 72189-153 TABLET 8 mg ORAL ANDA 16 sections
Ramelteon HUMAN PRESCRIPTION DRUG LABEL 1 72319-005 TABLET, FILM COATED 8 mg ORAL ANDA 28 sections