ramelteon 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | 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 µM/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

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 2.597 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 0.475 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 64.863 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 23.988 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 25.750 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 47.470 % High 1
herg hERG pIC50 4.554 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 9.120 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 62.661 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 13.930 % High 1
kinase-safety-class ACVR2B,AXL,BRAF,CAMK2B,CAMK2D,CDK5,CDK9,EIF2AK3,EPHB4,ERBB2,GRK2,ITK,MAPK7,NTRK2,PDK1,PDK2,PDK4,PRKDC,TEK 19
kinase-selectivity-class BRAF,PDK4 2
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 0.865 High 1
mh-clint Mouse hepatocyte intrinsic clearance 58.884 High 1
mppb Mouse plasma protein binding (% unbound) 30.340 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 2.679 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pld-class Phospholipidosis risk class (1 = positive, 0 = negative) 1 High 1
pppb Pig plasma protein binding (% unbound) 51.550 % High 1
rh-clint Rat hepatocyte intrinsic clearance 174.181 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 82.980 % High 1
rppb Rat plasma protein binding (% unbound) 25.880 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 508.159 uM High 1

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
Abnormal dreams 144.89 18.34 47 6467 11210 90610723
Nightmare 121.60 18.34 49 6465 21676 90600257
Initial insomnia 120.33 18.34 39 6475 9271 90612662
Middle insomnia 101.45 18.34 40 6474 16711 90605222
Somnolence 95.70 18.34 95 6419 208989 90412944
Product dispensing error 76.75 18.34 30 6484 12243 90609690
Altered state of consciousness 74.34 18.34 39 6475 31493 90590440
Hepatic function abnormal 60.42 18.34 39 6475 46249 90575684
Poor quality sleep 59.51 18.34 31 6483 24662 90597271
Restlessness 43.93 18.34 29 6485 35691 90586242
Intentional overdose 43.50 18.34 43 6471 93791 90528142
Hallucination 39.78 18.34 35 6479 65924 90556009
Feeling abnormal 36.31 18.34 52 6462 167183 90454750
Ovarian cancer recurrent 34.84 18.34 10 6504 1580 90620353
Somnambulism 34.66 18.34 14 6500 6214 90615719
Blood pressure decreased 32.28 18.34 33 6481 74862 90547071
Platelet count decreased 28.86 18.34 42 6472 136927 90485006
Drug eruption 28.03 18.34 22 6492 35385 90586548
Agitation 27.89 18.34 29 6485 67069 90554864
Product administered to patient of inappropriate age 27.77 18.34 11 6503 4642 90617291
Galactorrhoea 27.73 18.34 11 6503 4661 90617272
Anaemia 27.62 18.34 71 6443 352731 90269202
Interstitial lung disease 26.48 18.34 30 6484 76375 90545558
Fall 26.15 18.34 85 6429 481725 90140208
Hypersomnia 25.31 18.34 17 6497 21514 90600419
Pneumonia aspiration 25.23 18.34 22 6492 40918 90581015
Hallucination, visual 24.23 18.34 17 6497 23075 90598858
Hangover 23.59 18.34 8 6506 2181 90619752
Respiratory failure 21.65 18.34 34 6480 118384 90503549
Impulsive behaviour 21.34 18.34 7 6507 1723 90620210
Decreased appetite 20.92 18.34 67 6447 376473 90245460
Renal impairment 20.29 18.34 31 6483 105390 90516543
Infusion related reaction 20.11 18.34 3 6511 416777 90205156
Anxiety 19.89 18.34 58 6456 309714 90312219
Drug intolerance 19.89 18.34 4 6510 447587 90174346
Palpitations 19.33 18.34 35 6479 136693 90485240
Hypozincaemia 19.03 18.34 3 6511 24 90621909

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 70.27 17.18 83 4738 141022 42475492
Pneumonia aspiration 64.76 17.18 50 4771 50028 42566486
Initial insomnia 59.93 17.18 21 4800 4009 42612505
Hangover 51.80 17.18 14 4807 1124 42615390
Middle insomnia 49.60 17.18 22 4799 7811 42608703
Abnormal dreams 48.45 17.18 22 4799 8249 42608265
Hepatic function abnormal 46.88 17.18 42 4779 51525 42564989
Interstitial lung disease 45.49 17.18 50 4771 78412 42538102
Delirium 34.90 17.18 36 4785 52483 42564031
Disseminated intravascular coagulation 34.76 17.18 26 4795 24768 42591746
Nightmare 34.56 17.18 26 4795 24986 42591528
Altered state of consciousness 30.96 17.18 26 4795 29233 42587281
Poor quality sleep 28.40 17.18 16 4805 9424 42607090
Cerebral infarction 27.54 17.18 25 4796 31144 42585370
Marasmus 27.03 17.18 8 4813 891 42615623
Renal impairment 24.06 17.18 44 4777 110184 42506330
Product administered to patient of inappropriate age 22.74 17.18 11 4810 4750 42611764
Restlessness 21.15 17.18 21 4800 29228 42587286
Hyperuricaemia 20.60 17.18 13 4808 9411 42607103
Liver disorder 19.12 17.18 23 4798 39621 42576893
Pneumonia bacterial 18.81 17.18 15 4806 15677 42600837
Spinal compression fracture 18.07 17.18 11 4810 7472 42609042
Femoral neck fracture 17.94 17.18 9 4812 4200 42612314
Upper respiratory tract inflammation 17.62 17.18 7 4814 1889 42614625
Enterocolitis 17.56 17.18 12 4809 9917 42606597

FDA Adverse Event Reporting System (Geriatric)

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
Hepatic function abnormal 105.21 17.12 76 9564 89219 110490440
Somnolence 98.06 17.12 125 9515 297324 110282335
Pneumonia aspiration 95.37 17.12 69 9571 81164 110498495
Altered state of consciousness 94.00 17.12 60 9580 57566 110522093
Initial insomnia 93.87 17.12 35 9605 10354 110569305
Middle insomnia 80.02 17.12 38 9602 20464 110559195
Interstitial lung disease 68.47 17.12 72 9568 139262 110440397
Abnormal dreams 60.22 17.12 27 9613 12753 110566906
Poor quality sleep 57.96 17.12 34 9606 28043 110551616
Product administered to patient of inappropriate age 54.56 17.12 22 9618 8014 110571645
Restlessness 53.18 17.12 42 9598 56217 110523442
Hangover 52.96 17.12 16 9624 2486 110577173
Disseminated intravascular coagulation 43.77 17.12 33 9607 41253 110538406
Delirium 43.22 17.12 56 9584 134969 110444690
Marasmus 40.95 17.12 12 9628 1679 110577980
Drug eruption 40.17 17.12 35 9605 53624 110526035
Renal impairment 39.58 17.12 64 9576 188381 110391278
Femoral neck fracture 39.21 17.12 20 9620 12547 110567112
Cerebral infarction 39.18 17.12 34 9606 51804 110527855
Nightmare 38.86 17.12 30 9610 38833 110540826
Intentional overdose 37.87 17.12 52 9588 132449 110447210
Blood pressure decreased 34.15 17.12 46 9594 115045 110464614
Platelet count decreased 33.91 17.12 67 9573 230376 110349283
Arthralgia 31.99 17.12 14 9626 779618 109800041
Spinal compression fracture 29.60 17.12 19 9621 18373 110561286
Decreased appetite 28.78 17.12 99 9541 475747 110103912
Pneumonia bacterial 27.85 17.12 21 9619 26240 110553419
Anaemia 27.34 17.12 107 9533 546979 110032680
Cardiac failure acute 27.20 17.12 20 9620 24058 110555601
Hypersomnia 26.62 17.12 21 9619 28040 110551619
Hallucination 24.85 17.12 37 9603 101395 110478264
Fall 24.67 17.12 111 9529 603371 109976288
Respiratory failure 24.06 17.12 56 9584 215276 110364383
Hyperuricaemia 23.35 17.12 15 9625 14516 110565143
Feeling abnormal 22.42 17.12 49 9591 180662 110398997
Cardiac failure 22.29 17.12 50 9590 187576 110392083
Colon cancer 21.66 17.12 15 9625 16428 110563231
Renal disorder 21.53 17.12 24 9616 49455 110530204
Ileus 20.92 17.12 19 9621 30710 110548949
Dysphagia 20.61 17.12 43 9597 153557 110426102
Peripheral swelling 20.51 17.12 5 9635 404029 110175630
Gastroenteritis eosinophilic 19.98 17.12 5 9635 386 110579273
Upper respiratory tract inflammation 19.84 17.12 9 9631 4362 110575297
Somnambulism 19.42 17.12 10 9630 6395 110573264
Dyskinesia 19.10 17.12 23 9617 51423 110528236
Hallucination, visual 18.60 17.12 20 9620 39585 110540074
Stoma site hypergranulation 17.82 17.12 5 9635 599 110579060
Rhabdomyolysis 17.68 17.12 35 9605 120366 110459293

FDA Adverse Event Reporting System (Pediatric)

None

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

Related Drugs by ATC class:

N05CH Melatonin receptor agonists 2 drugs
melatonintasimelteon

Drug Use | Suggest Off label Use Form| |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




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

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
Sigma non-opioid intracellular receptor 1 Membrane receptor Ki 5.05 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
C495910 MESH_SUPPLEMENTAL_RECORD_UI
208902 PUBCHEM_CID
1356 IUPHAR_LIGAND_ID
8447 INN_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
Ramelteon HUMAN PRESCRIPTION DRUG LABEL 1 0904-7494 TABLET 8 mg ORAL ANDA 27 sections
Ramelteon HUMAN PRESCRIPTION DRUG LABEL 1 10135-838 TABLET, FILM COATED 8 mg ORAL ANDA 29 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 42571-375 TABLET 8 mg ORAL ANDA 25 sections
Ramelteon HUMAN PRESCRIPTION DRUG LABEL 1 43598-741 TABLET 8 mg ORAL ANDA 25 sections
Ramelteon HUMAN PRESCRIPTION DRUG LABEL 1 50268-822 TABLET 8 mg ORAL ANDA 25 sections
Ramelteon HUMAN PRESCRIPTION DRUG LABEL 1 50436-3980 TABLET, FILM COATED 8 mg ORAL ANDA 28 sections
Ramelteon HUMAN PRESCRIPTION DRUG LABEL 1 51407-523 TABLET, FILM COATED 8 mg ORAL ANDA 27 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 59651-505 TABLET, FILM COATED 8 mg ORAL ANDA 26 sections
Ramelteon HUMAN PRESCRIPTION DRUG LABEL 1 60687-692 TABLET 8 mg ORAL ANDA 26 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 70518-4257 TABLET, FILM COATED 8 mg ORAL ANDA 29 sections
Ramelteon HUMAN PRESCRIPTION DRUG LABEL 1 70700-272 TABLET, FILM COATED 8 mg ORAL ANDA 27 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 2 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 71335-2186 TABLET, FILM COATED 8 mg ORAL ANDA 28 sections
Ramelteon HUMAN PRESCRIPTION DRUG LABEL 1 71335-2310 TABLET 8 mg ORAL ANDA 25 sections
RAMELTEON HUMAN PRESCRIPTION DRUG LABEL 1 71335-2411 TABLET, FILM COATED 8 mg ORAL ANDA 26 sections
Ramelteon HUMAN PRESCRIPTION DRUG LABEL 1 71335-2886 TABLET, FILM COATED 8 mg ORAL ANDA 28 sections