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Showing metabocard for Ramelteon (HMDB0015115)

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IdentificationTaxonomyOntologyPhysical propertiesSpectraBiological propertiesConcentrationsLinksReferencesenzymes (5) Show 5 proteinsXML
enzymes (5) Show 5 proteins
Record Information
Version4.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:51 UTC
Update Date2020-02-26 21:41:00 UTC
HMDB IDHMDB0015115
Secondary Accession Numbers
  • HMDB15115
Metabolite Identification
Common NameRamelteon
DescriptionRamelteon, also known as rozerem or TAK-375, belongs to the class of organic compounds known as indanes. Indanes are compounds containing an indane moiety, which consists of a cyclopentane fused to a benzene ring. Ramelteon is the first in a new class of sleep agents that selectively binds to the melatonin receptors in the suprachiasmatic nucleus (SCN). Ramelteon is a drug which is used for the treatment of insomnia characterized by difficulty with sleep onset. Ramelteon is a melatonin receptor agonist with both high affinity for melatonin MT1 and MT2 receptors, and lower selectivity for the MT3 receptor. Ramelteon is an extremely weak basic (essentially neutral) compound (based on its pKa). Ramelteon has a high affinity for the MT1 and MT2 receptors. The metabolite also has weak affinity for the 5HT2b receptor. Ramelteon has not been shown to produce dependence and has shown no potential for abuse. 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. It is used for insomnia, particularly delayed sleep onset.
Structure
Data?1582753260
MOLSDFPDBSMILESInChI
Synonyms
ValueSource
RozeremKegg
TAK-375HMDB
(S)-N-(2-(1,6,7,8-Tetrahydro-2H-indeno-(5,4)furan-8-yl)ethyl)propionamideHMDB
Chemical FormulaC16H21NO2
Average Molecular Weight259.3434
Monoisotopic Molecular Weight259.157228921
IUPAC NameN-{2-[(8S)-1H,2H,6H,7H,8H-indeno[5,4-b]furan-8-yl]ethyl}propanamide
Traditional Nameramelteon
CAS Registry Number196597-26-9
SMILES
CCC(=O)NCC[C@@H]1CCC2=C1C1=C(OCC1)C=C2
InChI Identifier
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
InChI KeyYLXDSYKOBKBWJQ-LBPRGKRZSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as indanes. Indanes are compounds containing an indane moiety, which consists of a cyclopentane fused to a benzene ring.
KingdomOrganic compounds
Super ClassBenzenoids
ClassIndanes
Sub ClassNot Available
Direct ParentIndanes
Alternative Parents
Substituents
  • Indane
  • Coumaran
  • Alkyl aryl ether
  • Carboxamide group
  • Secondary carboxylic acid amide
  • Oxacycle
  • Organoheterocyclic compound
  • Ether
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organic oxygen compound
  • Organic nitrogen compound
  • Carbonyl group
  • Organopnictogen compound
  • Organic oxide
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Ontology
Disposition

Biological location:

Role

Industrial application:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.016 g/LNot Available
LogP2.4Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.016 g/LALOGPS
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 ŲChemAxon
Rotatable Bond Count4ChemAxon
Refractivity75.52 m³·mol⁻¹ChemAxon
Polarizability29.99 ųChemAxon
Number of Rings3ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0a7r-9870000000-1c290026ffceb3eef315Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0nmi-2980000000-5ee1e7ec83e5c4578dfeSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0w29-0190000000-5ab5aa60e4a12e68a700Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0uki-2950000000-2f78e21b2259ce9f7f74Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a4i-1900000000-72904ed8a2217e0540cfSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-1090000000-86053c1f7ca9207210fdSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0ab9-6290000000-07567898b89338a73662Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00dl-9200000000-fd494970ea1477bf6bffSpectrum
Biological Properties
Cellular Locations
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00980 details
UrineExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00980 details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00980
Phenol Explorer Compound IDNot Available
FooDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID181000
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkRamelteon
METLIN IDNot Available
PubChem Compound208902
PDB IDNot Available
ChEBI ID321962
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB ID
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. 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 ]
  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. Borja NL, Daniel KL: Ramelteon for the treatment of insomnia. Clin Ther. 2006 Oct;28(10):1540-55. [PubMed:17157111 ]
  4. Simpson D, Curran MP: Ramelteon: a review of its use in insomnia. Drugs. 2008;68(13):1901-19. [PubMed:18729542 ]
  5. 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 ]
  6. 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 ]

Enzymes

Enzyme Details
1. Cytochrome P450 3A4
General function:
Involved in monooxygenase 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 xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular weight:
57255.585
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 ]
Enzyme Details
2. Cytochrome P450 2C19
General function:
Involved in monooxygenase 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:
55944.565
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 ]
Enzyme Details
3. Cytochrome P450 1A2
General function:
Involved in monooxygenase 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 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 N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen. Participates in the bioactivation of carcinogenic aromatic and heterocyclic amines. Catalizes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin.
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular weight:
58406.915
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 ]
Enzyme Details
4. Melatonin receptor type 1A
General function:
Involved in G-protein coupled receptor protein signaling pathway
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:
39374.3
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 ]
Enzyme Details
5. Melatonin receptor type 1B
General function:
Involved in G-protein coupled receptor protein signaling pathway
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:
40187.9
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 ]