Identification
- Summary
Tasimelteon is a melatonin receptor agonist used to treat Non- 24-Hour Sleep-Wake Disorder.
- Brand Names
- Hetlioz
- Generic Name
- Tasimelteon
- DrugBank Accession Number
- DB09071
- Background
Tasimelteon is a selective dual melatonin receptor agonist indicated for the treatment of Non-24-Hour Sleep-Wake Disorder (N24HSWD). Occurring commonly in blind individuals without light perception, this condition is often characterized by periods of night-time insomnia and day-time sleepiness. In blind individuals, a lack of light stimulation causes an extension of the 24-hour circadian cycle and can lead to progressively delayed sleep onset. By activating melatonin receptors MT1 and MT2 in the suprachiasmatic nucleus of the brain, tasimelteon has been shown to improve sleep by resynchronizing the circadian rhythm through its "non-photic" mechanism. Tasimelteon is currently the only drug available for the treatment of N24HSWD and was granted orphan drug status by the FDA in 2010.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Tasimelteon (DB09071)
- Weight
- Average: 245.322
Monoisotopic: 245.141578856 - Chemical Formula
- C15H19NO2
- Synonyms
- N-{[(1R,2R)-2-(2,3-dihydro-1-benzofuran-4-yl)cyclopropyl]methyl}propanamide
- Tasimeltéon
- Tasimelteon
- Tasimelteón
- Tasimelteonum
- External IDs
- BMS 214778
- BMS-214,778
- BMS-214778
- BMS214778
- VEC 162
- VEC-162
- VEC162
Pharmacology
- Indication
Tasimelteon oral capsules are indicated for the treatment of non-24 hour sleep-wake disorder in adult patients and for the treatment of nighttime sleep disturbances in Smith-Magenis Syndrome in patients ≥16 years old.5 Tasimelteon oral suspension is indicated for the treatment of nighttime sleep disturbances in Smith-Magenis syndrome in patients 3 to 15 years of age.5
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Management of Non-24-hour sleep-wake disorder •••••••••••• ••••• ••••••• Management of Sleep disturbance •••••••••••• •••••••••• Management of Sleep disturbance •••••••••••• ••••••• - Contraindications & Blackbox Warnings
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Not Available
- Mechanism of action
Tasimelteon is a selective dual agonist of the melatonin receptors MT1 and MT2.
Target Actions Organism AMelatonin receptor type 1A agonistHumans AMelatonin receptor type 1B agonistHumans - Absorption
Not Available
- Volume of distribution
The apparent oral volume of distribution of tasimelteon at steady state in young healthy subjects is approximately 56 - 126 L.
- Protein binding
At therapeutic concentrations, tasimelteon is about 90% bound to proteins.
- Metabolism
Tasimelteon is extensively metabolized. Metabolism of tasimelteon consists primarily of oxidation at multiple sites and oxidative dealkylation resulting in opening of the dihydrofuran ring followed by further oxidation to give a carboxylic acid. CYP1A2 and CYP3A4 are the major isozymes involved in the metabolism of tasimelteon. Phenolic glucuronidation is the major phase II metabolic route.
- Route of elimination
Following oral administration of radiolabeled tasimelteon, 80% of total radioactivity was excreted in urine and approximately 4% in feces, resulting in a mean recovery of 84%. Less than 1% of the dose was excreted in urine as the parent compound.
- Half-life
The observed mean elimination half-life for tasimelteon is 1.3 ± 0.4 hours.
- Clearance
Not Available
- Adverse Effects
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The most common adverse reactions are headache, increased alanine aminotransferase, nightmares or unusual dreams, and upper respiratory or urinary tract infections. There are currently no adequate or well-controlled studies that suggest that tasimelteon is safe to use during pregnancy. In animal studies, administration of tasimelteon during pregnancy resulted in developmental toxicity (embryofetal mortality, neurobehavioral impairment, and decreased growth and development in offspring) at doses greater than those used clinically. During clinical trials, rats did not self-administer tasimelteon, suggesting that the drug does not have a potential for abuse.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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 Tasimelteon is combined with 1,2-Benzodiazepine. Abacavir Abacavir may decrease the excretion rate of Tasimelteon which could result in a higher serum level. Abametapir The serum concentration of Tasimelteon can be increased when it is combined with Abametapir. Abatacept The metabolism of Tasimelteon can be increased when combined with Abatacept. Abemaciclib The metabolism of Abemaciclib can be decreased when combined with Tasimelteon. - Food Interactions
- Avoid grapefruit products. Grapefruit inhibits the CYP3A4 metabolism of tasimelteon, which may increase its serum concentration. Alternatively, the dose of tasimelteon may need to be modified.
- Avoid St. John's Wort. This herb induces the CYP3A4 metabolism of tasimelteon and may reduce its serum concentration. Alternatively, the dose of tasimelteon may need to be modified.
- Take on an empty stomach. The Cmax of tasimelteon is reduced when taken with food.
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.- International/Other Brands
- Hetlioz
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Hetlioz Capsule 20 mg/1 Oral Vanda Pharmaceuticals Inc. 2014-04-04 Not applicable US 
Hetlioz Capsule 20 mg Oral Vanda Pharmaceuticals Netherlands B.V. 2016-09-08 Not applicable EU 
Hetlioz LQ Suspension 4 mg/1mL Oral Vanda Pharmaceuticals Inc. 2020-12-10 Not applicable US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Tasimelteon Capsule 20 mg/1 Oral Amneal Pharmaceuticals NY LLC 2023-02-24 Not applicable US Tasimelteon Capsule, gelatin coated 20 mg/1 Oral Teva Pharmaceuticals, Inc. 2022-12-29 Not applicable US Tasimelteon Capsule 20 mg/1 Oral Apotex Corp. 2024-01-05 Not applicable US
Categories
- ATC Codes
- N05CH03 — Tasimelteon
- Drug Categories
- Central Nervous System Depressants
- Cycloparaffins
- Cytochrome P-450 CYP1A2 Substrates
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A4 Substrates (strength unknown)
- Cytochrome P-450 Substrates
- Drugs that are Mainly Renally Excreted
- Heterocyclic Compounds, Fused-Ring
- Hypnotics and Sedatives
- Melatonin Receptor Agonists
- Nervous System
- Psycholeptics
- Receptors, Melatonin, agonists
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as coumarans. These are compounds containing the coumaran skeleton, which consists of a benzene ring fused to a 2,3-dihydrofuran ring.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Coumarans
- Sub Class
- Not Available
- Direct Parent
- Coumarans
- Alternative Parents
- Alkyl aryl ethers / Benzenoids / Secondary carboxylic acid amides / Oxacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
- Substituents
- Alkyl aryl ether / Aromatic heteropolycyclic compound / Benzenoid / Carbonyl group / Carboxamide group / Carboxylic acid derivative / Coumaran / Ether / Hydrocarbon derivative / Organic nitrogen compound
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- monocarboxylic acid amide, 1-benzofurans, cyclopropanes (CHEBI:79042)
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- SHS4PU80D9
- CAS number
- 609799-22-6
- InChI Key
- PTOIAAWZLUQTIO-GXFFZTMASA-N
- InChI
- InChI=1S/C15H19NO2/c1-2-15(17)16-9-10-8-13(10)11-4-3-5-14-12(11)6-7-18-14/h3-5,10,13H,2,6-9H2,1H3,(H,16,17)/t10-,13+/m0/s1
- IUPAC Name
- N-{[(1R,2R)-2-(2,3-dihydro-1-benzofuran-4-yl)cyclopropyl]methyl}propanamide
- SMILES
- CCC(=O)NC[C@@H]1C[C@H]1C1=CC=CC2=C1CCO2
References
- General References
- Lavedan C, Forsberg M, Gentile AJ: Tasimelteon: a selective and unique receptor binding profile. Neuropharmacology. 2015 Apr;91:142-7. doi: 10.1016/j.neuropharm.2014.12.004. Epub 2014 Dec 19. [Article]
- Neubauer DN: Tasimelteon for the treatment of non-24-hour sleep-wake disorder. Drugs Today (Barc). 2015 Jan;51(1):29-35. doi: 10.1358/dot.2015.51.1.2258364. [Article]
- Stahl SM: Mechanism of action of tasimelteon in non-24 sleep-wake syndrome: treatment for a circadian rhythm disorder in blind patients. CNS Spectr. 2014 Dec;19(6):475-8. doi: 10.1017/S1092852914000637. [Article]
- Vachharajani NN, Yeleswaram K, Boulton DW: Preclinical pharmacokinetics and metabolism of BMS-214778, a novel melatonin receptor agonist. J Pharm Sci. 2003 Apr;92(4):760-72. [Article]
- FDA Approved Drug Products: Hetlioz (tasimelteon) capsules/suspension for oral use [Link]
- External Links
- KEGG Drug
- D09388
- PubChem Compound
- 10220503
- PubChem Substance
- 310265003
- ChemSpider
- 8395995
- 1490468
- ChEBI
- 79042
- ChEMBL
- CHEMBL2103822
- ZINC
- ZINC000004392649
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Tasimelteon
- FDA label
- Download (249 KB)
- MSDS
- Download (203 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Completed Basic Science Non 24 Hour Sleep Wake Disorder 1 3 Completed Treatment Insomnia 1 3 Completed Treatment Jet Lag Type Insomnia 1 3 Completed Treatment Non 24 Hour Sleep Wake Disorder 3 3 Completed Treatment Primary Insomnia 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Capsule Oral 20 mg/1 Capsule Oral 20 MG Suspension Oral 4 mg/1mL Capsule, gelatin coated Oral 20 mg/1 - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US5856529 No 1999-01-05 2017-12-09 US US8785492 No 2014-07-22 2033-01-25 US US9060995 No 2015-06-23 2033-01-25 US US9549913 No 2017-01-24 2033-01-25 US US9539234 No 2017-01-10 2033-01-25 US US9730910 No 2017-08-15 2034-05-17 US USRE46604 No 2017-11-14 2033-01-25 US US9855241 No 2018-01-02 2033-01-25 US US10071977 No 2018-09-11 2035-02-12 US US10149829 No 2018-12-11 2033-01-25 US US10449176 No 2019-10-22 2033-01-25 US US10376487 No 2019-08-13 2035-07-27 US US10610510 No 2020-04-07 2033-01-25 US US10610511 No 2020-04-07 2034-10-10 US US10179119 No 2019-01-15 2035-08-29 US US10829465 No 2020-11-10 2035-02-12 US US10945988 No 2021-03-16 2033-01-25 US US10980770 No 2021-04-20 2033-01-25 US US11141400 No 2021-10-12 2034-10-10 US US11202770 No 2021-12-21 2040-12-11 US US11285129 No 2013-01-25 2033-01-25 US US11266622 No 2015-08-29 2035-08-29 US US11566011 No 2015-02-12 2035-02-12 US US11633377 No 2013-01-25 2033-01-25 US US11759446 No 2021-02-21 2041-02-21 US US11760740 No 2015-02-12 2035-02-12 US US11786502 No 2014-10-10 2034-10-10 US US11833130 No 2013-01-25 2033-01-25 US US11850229 No 2013-01-25 2033-01-25 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source boiling point (°C) 442.553°C MSDS water solubility 1.1 mg/mL MSDS logP 2.43 MSDS - Predicted Properties
Property Value Source Water Solubility 0.0381 mg/mL ALOGPS logP 2.53 ALOGPS logP 1.98 Chemaxon logS -3.8 ALOGPS pKa (Strongest Acidic) 15.74 Chemaxon pKa (Strongest Basic) -1.2 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 70.35 m3·mol-1 Chemaxon Polarizability 27.52 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
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-05o9-6930000000-682ef7912fba17288319 Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-00dl-4920000000-b23940a679632930ba28 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0006-0290000000-e877da628598febb722e Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-052f-3920000000-72315e7fbe87f367a5e9 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-05fr-4920000000-e15e23a6b5767a0592f0 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0ab9-4910000000-4b637148c8e16711176e Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-066u-9710000000-14f3a334ee9b78af866d Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 171.5970683 predictedDarkChem Lite v0.1.0 [M-H]- 157.23802 predictedDeepCCS 1.0 (2019) [M+H]+ 172.0549683 predictedDarkChem Lite v0.1.0 [M+H]+ 159.6337 predictedDeepCCS 1.0 (2019) [M+Na]+ 171.8840683 predictedDarkChem Lite v0.1.0 [M+Na]+ 165.90906 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Organic cyclic compound binding
- 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 ...
- Gene Name
- MTNR1A
- Uniprot ID
- P48039
- Uniprot Name
- Melatonin receptor type 1A
- Molecular Weight
- 39374.315 Da
References
- Lavedan C, Forsberg M, Gentile AJ: Tasimelteon: a selective and unique receptor binding profile. Neuropharmacology. 2015 Apr;91:142-7. doi: 10.1016/j.neuropharm.2014.12.004. Epub 2014 Dec 19. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Melatonin receptor activity
- 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 ...
- Gene Name
- MTNR1B
- Uniprot ID
- P49286
- Uniprot Name
- Melatonin receptor type 1B
- Molecular Weight
- 40187.895 Da
References
- Lavedan C, Forsberg M, Gentile AJ: Tasimelteon: a selective and unique receptor binding profile. Neuropharmacology. 2015 Apr;91:142-7. doi: 10.1016/j.neuropharm.2014.12.004. Epub 2014 Dec 19. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Vitamin d3 25-hydroxylase 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 react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Ogilvie BW, Torres R, Dressman MA, Kramer WG, Baroldi P: Clinical assessment of drug-drug interactions of tasimelteon, a novel dual melatonin receptor agonist. J Clin Pharmacol. 2015 Sep;55(9):1004-11. doi: 10.1002/jcph.507. Epub 2015 May 7. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
- 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 un...
- Gene Name
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58293.76 Da
References
Drug created at May 14, 2015 16:07 / Updated at March 10, 2022 09:37