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Identification
- Summary
Ramelteon is a melatonin receptor agonist used to treat insomnia.
- Brand Names
- Rozerem
- Generic Name
- Ramelteon
- DrugBank Accession Number
- DB00980
- Background
Ramelteon 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.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Ramelteon (DB00980)
- Weight
- Average: 259.3434
Monoisotopic: 259.157228921 - Chemical Formula
- C16H21NO2
- Synonyms
- Ramelteon
- External IDs
- TAK-375
- TAK375
Pharmacology
- Indication
For the treatment of insomnia characterized by difficulty with sleep onset.
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Management of Insomnia •••••••••••• - Contraindications & Blackbox Warnings
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Ramelteon 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 action
Ramelteon 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.
Target Actions Organism AMelatonin receptor type 1B multitargetHumans AMelatonin receptor type 1A multitargetHumans - Absorption
Rapid, total absorption is at least 84%.
- Volume of distribution
- 73.6 L
- Protein binding
~82% (in human serum)
- Metabolism
Hepatic
- Route of elimination
Following 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
- Clearance
Not Available
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The risk or severity of CNS depression can be increased when Ramelteon is combined with 1,2-Benzodiazepine. Abacavir Ramelteon may decrease the excretion rate of Abacavir which could result in a higher serum level. Abametapir The serum concentration of Ramelteon can be increased when it is combined with Abametapir. Abatacept The metabolism of Ramelteon can be increased when combined with Abatacept. Abiraterone The serum concentration of Ramelteon can be increased when it is combined with Abiraterone. - Food Interactions
- Avoid alcohol.
- Do not take with or immediately after a high-fat meal.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Images
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Rozerem Tablet, film coated 8 mg/1 Oral Avera McKennan Hospital 2015-03-05 2017-05-24 US 
Rozerem Tablet, film coated 8 mg/1 Oral Lake Erie Medical Dba Quality Care Produts Llc 2011-05-18 2017-06-01 US Rozerem Tablet, film coated 8 mg/1 Oral Takeda Pharma A/S 2005-07-22 Not applicable US 
Rozerem Tablet, film coated 8 mg/1 Oral Rebel Distributors 2005-07-22 Not applicable US 
Rozerem Tablet, film coated 8 mg/1 Oral bryant ranch prepack 2005-07-22 2015-10-30 US 
- Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Ramelteon Tablet, film coated 8 mg/1 Oral Unit Dose Services 2020-06-30 Not applicable US Ramelteon Tablet, film coated 8 mg/1 Oral bryant ranch prepack 2020-06-30 Not applicable US Ramelteon Tablet, film coated 8 mg/1 Oral i3 Pharmaceuticals, LLC 2020-04-30 Not applicable US Ramelteon Tablet 8 mg/1 Oral Proficient Rx LP 2020-10-01 Not applicable US Ramelteon Tablet, film coated 8 mg/1 Oral Aurobindo Pharma (Italia) S.R.L. 2023-07-10 Not applicable US
Categories
- ATC Codes
- N05CH02 — Ramelteon
- Drug Categories
- Central Nervous System Depressants
- Cytochrome P-450 CYP1A2 Substrates
- Cytochrome P-450 CYP2C19 Substrates
- Cytochrome P-450 CYP2C9 Substrates
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- Drugs that are Mainly Renally Excreted
- Hypnotics and Sedatives
- Melatonin Receptor Agonists
- Nervous System
- Psycholeptics
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as indanes. These are compounds containing an indane moiety, which consists of a cyclopentane fused to a benzene ring.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Indanes
- Sub Class
- Not Available
- Direct Parent
- Indanes
- Alternative Parents
- Coumarans / Alkyl aryl ethers / Secondary carboxylic acid amides / Oxacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
- Substituents
- Alkyl aryl ether / Aromatic heteropolycyclic compound / Carbonyl group / Carboxamide group / Carboxylic acid derivative / Coumaran / Ether / Hydrocarbon derivative / Indane / Organic nitrogen compound
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 901AS54I69
- CAS number
- 196597-26-9
- InChI Key
- YLXDSYKOBKBWJQ-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
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
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Borja NL, Daniel KL: Ramelteon for the treatment of insomnia. Clin Ther. 2006 Oct;28(10):1540-55. [Article]
- 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. [Article]
- Simpson D, Curran MP: Ramelteon: a review of its use in insomnia. Drugs. 2008;68(13):1901-19. [Article]
- External Links
- Human Metabolome Database
- HMDB0015115
- PubChem Compound
- 208902
- PubChem Substance
- 46505923
- ChemSpider
- 181000
- BindingDB
- 50118470
- 596205
- ChEBI
- 109549
- ChEMBL
- CHEMBL1218
- ZINC
- ZINC000003960338
- Therapeutic Targets Database
- DAP000070
- PharmGKB
- PA164744896
- Guide to Pharmacology
- GtP Drug Page
- PDBe Ligand
- JEV
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Ramelteon
- PDB Entries
- 6me2 / 6me9 / 7db6 / 7vgz / 7vh0
- FDA label
- Download (2.36 MB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Completed Not Available Insomnia 2 somestatus stop reason just information to hide Not Available Completed Basic Science Healthy Volunteers (HV) 1 somestatus stop reason just information to hide Not Available Completed Diagnostic Obstructive Sleep Apnea (OSA) 1 somestatus stop reason just information to hide Not Available Terminated Treatment Insomnia / Panic Disorder 1 somestatus stop reason just information to hide Not Available Terminated Treatment Neuropathic Pain 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Takeda global research development center inc
- Packagers
- Bryant Ranch Prepack
- DispenseXpress Inc.
- Innoviant Pharmacy Inc.
- Physicians Total Care Inc.
- Rebel Distributors Corp.
- Southwood Pharmaceuticals
- Takeda Pharmaceutical Co. Ltd.
- Dosage Forms
Form Route Strength Tablet, film coated Oral 8 mg Tablet Oral 8 mg/1 Tablet, coated Oral 8 mg/1 Tablet, film coated Oral 8 mg/1 - Prices
Unit description Cost Unit Rozerem 8 mg tablet 5.17USD tablet DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US6034239 No 2000-03-07 2019-07-22 US US10098866 No 2018-10-16 2021-11-16 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source logP 2.4 Not Available - Predicted Properties
Property Value Source Water Solubility 0.0164 mg/mL ALOGPS logP 3.03 ALOGPS logP 2.57 Chemaxon logS -4.2 ALOGPS pKa (Strongest Acidic) 15.82 Chemaxon pKa (Strongest Basic) -1.4 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 38.33 Å2 Chemaxon Rotatable Bond Count 4 Chemaxon Refractivity 75.52 m3·mol-1 Chemaxon Polarizability 29.99 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule Yes Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 1.0 Blood Brain Barrier + 0.9934 Caco-2 permeable + 0.5893 P-glycoprotein substrate Substrate 0.5211 P-glycoprotein inhibitor I Non-inhibitor 0.8548 P-glycoprotein inhibitor II Non-inhibitor 0.7877 Renal organic cation transporter Non-inhibitor 0.6381 CYP450 2C9 substrate Non-substrate 0.7876 CYP450 2D6 substrate Non-substrate 0.6392 CYP450 3A4 substrate Substrate 0.512 CYP450 1A2 substrate Inhibitor 0.7314 CYP450 2C9 inhibitor Non-inhibitor 0.6471 CYP450 2D6 inhibitor Non-inhibitor 0.5916 CYP450 2C19 inhibitor Inhibitor 0.8314 CYP450 3A4 inhibitor Non-inhibitor 0.9196 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.7763 Ames test Non AMES toxic 0.7016 Carcinogenicity Non-carcinogens 0.8206 Biodegradation Ready biodegradable 0.6635 Rat acute toxicity 2.1034 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.7898 hERG inhibition (predictor II) Inhibitor 0.5
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 170.1634556 predictedDarkChem Lite v0.1.0 [M-H]- 160.3073 predictedDeepCCS 1.0 (2019) [M+H]+ 170.8073556 predictedDarkChem Lite v0.1.0 [M+H]+ 162.66527 predictedDeepCCS 1.0 (2019) [M+Na]+ 170.2596556 predictedDarkChem Lite v0.1.0 [M+Na]+ 168.75844 predictedDeepCCS 1.0 (2019)
Targets
Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Multitarget
- General Function
- High affinity receptor for melatonin. Likely to mediate 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
- Specific Function
- G protein-coupled receptor activity
- Gene Name
- MTNR1B
- Uniprot ID
- P49286
- Uniprot Name
- Melatonin receptor type 1B
- Molecular Weight
- 40187.895 Da
References
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Authors unspecified: Ramelteon: TAK 375. Drugs R D. 2005;6(3):186-8. [Article]
- 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. [Article]
- Miyamoto M: [A novel therapeutic drug: ramelteon]. Nihon Rinsho. 2009 Aug;67(8):1595-600. [Article]
- 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. [Article]
- Borja NL, Daniel KL: Ramelteon for the treatment of insomnia. Clin Ther. 2006 Oct;28(10):1540-55. [Article]
- 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. [Article]
- 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. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Multitarget
- General Function
- High affinity receptor for melatonin. Likely to mediate 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
- Specific Function
- G protein-coupled receptor activity
- Gene Name
- MTNR1A
- Uniprot ID
- P48039
- Uniprot Name
- Melatonin receptor type 1A
- Molecular Weight
- 39374.315 Da
References
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Authors unspecified: Ramelteon: TAK 375. Drugs R D. 2005;6(3):186-8. [Article]
- 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. [Article]
- Miyamoto M: [A novel therapeutic drug: ramelteon]. Nihon Rinsho. 2009 Aug;67(8):1595-600. [Article]
- 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. [Article]
- Borja NL, Daniel KL: Ramelteon for the treatment of insomnia. Clin Ther. 2006 Oct;28(10):1540-55. [Article]
- 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. [Article]
- 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. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of polyunsaturated fatty acids (PUFA) (PubMed:18577768, PubMed:19965576, PubMed:20972997). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18577768, PubMed:19965576, PubMed:20972997). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates PUFA specifically at the omega-1 position (PubMed:18577768). Catalyzes the epoxidation of double bonds of PUFA (PubMed:19965576, PubMed:20972997). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). 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. Hydroxylates fenbendazole at the 4' position (PubMed:23959307)
- Specific Function
- (R)-limonene 6-monooxygenase activity
- Gene Name
- CYP2C19
- Uniprot ID
- P33261
- Uniprot Name
- Cytochrome P450 2C19
- Molecular Weight
- 55944.565 Da
References
- 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. [Article]
- Pandi-Perumal SR, Spence DW, Verster JC, Srinivasan V, Brown GM, Cardinali DP, Hardeland R: Pharmacotherapy of insomnia with ramelteon: safety, efficacy and clinical applications. J Cent Nerv Syst Dis. 2011 Apr 12;3:51-65. doi: 10.4137/JCNSD.S1611. Print 2011. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids and steroids (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:15766564, PubMed:19965576, PubMed:7574697, PubMed:9866708). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Exhibits low catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes bisallylic hydroxylation and hydroxylation with double-bond migration of polyunsaturated fatty acids (PUFA) (PubMed:9435160, PubMed:9866708). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan (PubMed:25994031)
- Specific Function
- (R)-limonene 6-monooxygenase activity
- Gene Name
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:11555828, PubMed:12865317). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2 (PubMed:11555828, PubMed:12865317). Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). May act as a major enzyme for all-trans retinoic acid biosynthesis in the liver. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:10681376). Primarily catalyzes stereoselective epoxidation of the last double bond of polyunsaturated fatty acids (PUFA), displaying a strong preference for the (R,S) stereoisomer (PubMed:19965576). Catalyzes bisallylic hydroxylation and omega-1 hydroxylation of PUFA (PubMed:9435160). May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent) (PubMed:21068195). Plays a role in the oxidative metabolism of xenobiotics. Catalyzes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin (PubMed:14725854). Metabolizes caffeine via N3-demethylation (Probable)
- Specific Function
- aromatase activity
- Gene Name
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58406.915 Da
References
- 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. [Article]
- Neubauer DN: A review of ramelteon in the treatment of sleep disorders. Neuropsychiatr Dis Treat. 2008 Feb;4(1):69-79. [Article]
- Ramelteon FDA label [File]
Drug created at June 13, 2005 13:24 / Updated at June 02, 2024 21:47