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 127.71 17.48 38 5067 5117 53338844
Abnormal dreams 126.86 17.48 45 5060 10556 53333405
Nightmare 114.30 17.48 48 5057 17703 53326258
Middle insomnia 107.76 17.48 40 5065 10668 53333293
Product dispensing error 66.92 17.48 28 5077 10212 53333749
Somnolence 66.58 17.48 81 5024 167653 53176308
Poor quality sleep 61.53 17.48 31 5074 17292 53326669
Insomnia 59.57 17.48 81 5024 186991 53156970
Altered state of consciousness 36.26 17.48 25 5080 24811 53319150
Ovarian cancer recurrent 35.10 17.48 10 5095 1153 53342808
Hallucination 33.51 17.48 33 5072 53805 53290156
Hepatic function abnormal 31.51 17.48 27 5078 36872 53307089
Somnambulism 29.46 17.48 13 5092 5389 53338572
Intentional overdose 29.12 17.48 34 5071 67171 53276790
Restlessness 29.11 17.48 23 5082 28064 53315897
Galactorrhoea 26.35 17.48 11 5094 3984 53339977
Hangover 24.48 17.48 8 5097 1460 53342501
Feeling abnormal 24.11 17.48 45 5060 135256 53208705
Hypersomnia 22.78 17.48 16 5089 16339 53327622
Drug eruption 22.73 17.48 19 5086 25075 53318886
Impulsive behaviour 20.25 17.48 7 5098 1517 53342444
Blood pressure decreased 19.94 17.48 27 5078 61842 53282119
Anxiety 19.77 17.48 52 5053 196652 53147309
Hallucination, visual 18.61 17.48 15 5090 18817 53325144
Interstitial lung disease 18.01 17.48 25 5080 58597 53285364

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 67.33 18.87 70 3599 103727 32406130
Initial insomnia 65.59 18.87 21 3648 3051 32506806
Hangover 52.32 18.87 14 3655 1085 32508772
Middle insomnia 50.28 18.87 21 3648 6463 32503394
Nightmare 49.99 18.87 26 3643 13140 32496717
Abnormal dreams 47.78 18.87 22 3647 8542 32501315
Pneumonia aspiration 42.50 18.87 36 3633 41120 32468737
Interstitial lung disease 37.05 18.87 41 3628 64960 32444897
Poor quality sleep 36.65 18.87 18 3651 8056 32501801
Hepatic function abnormal 34.05 18.87 33 3636 44807 32465050
Delirium 30.81 18.87 31 3638 44015 32465842
Disseminated intravascular coagulation 29.68 18.87 23 3646 23153 32486704
Cerebral infarction 28.17 18.87 24 3645 27590 32482267
Upper respiratory tract inflammation 24.60 18.87 9 3660 1948 32507909
Restlessness 22.12 18.87 20 3649 24861 32484996
Insomnia 19.43 18.87 38 3631 100310 32409547

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 1A GPCR AGONIST Ki 10.90 WOMBAT-PK CHEMBL
Melatonin receptor type 1B GPCR AGONIST Ki 10.39 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
8447 INN_ID
C495910 MESH_SUPPLEMENTAL_RECORD_UI
208902 PUBCHEM_CID
1356 IUPHAR_LIGAND_ID
901AS54I69 UNII
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 71205-918 TABLET 8 mg ORAL ANDA 26 sections
Ramelteon HUMAN PRESCRIPTION DRUG LABEL 1 71335-1853 TABLET 8 mg ORAL ANDA 27 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