You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NameTasimelteon
Accession NumberDB09071
TypeSmall Molecule
GroupsApproved
Description

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.

Structure
Thumb
Synonyms
N-{[(1R,2R)-2-(2,3-dihydro-1-benzofuran-4-yl)cyclopropyl]methyl}propanamide
tasimeltéon
External Identifiers
  • BMS 214778
  • BMS-214778
  • BMS214778
  • VEC 162
  • VEC-162
  • VEC162
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Hetliozcapsule20 mg/1oralVanda Pharmaceuticals Inc.2014-04-04Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNIISHS4PU80D9
CAS number609799-22-6
WeightAverage: 245.322
Monoisotopic: 245.141578856
Chemical FormulaC15H19NO2
InChI KeyPTOIAAWZLUQTIO-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}propanimidic acid
SMILES
[H][C@@]1(CN=C(O)CC)C[C@@]1([H])C1=C2CCOC2=CC=C1
Taxonomy
ClassificationNot classified
Pharmacology
IndicationTasimelteon is indicated for the treatment of Non-24-Hour Sleep-Wake Disorder (N24HSWD).
PharmacodynamicsNot Available
Mechanism of actionTasimelteon is a selective dual agonist of the melatonin receptors MT1 and MT2.
Related Articles
AbsorptionNot 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 bindingAt 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 eliminationFollowing 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 lifeThe observed mean elimination half-life for tasimelteon is 1.3 ± 0.4 hours.
ClearanceNot Available
ToxicityThe 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.
Affected organismsNot Available
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal AbsorptionNot AvailableNot Available
Blood Brain BarrierNot AvailableNot Available
Caco-2 permeableNot AvailableNot Available
P-glycoprotein substrateNot AvailableNot Available
P-glycoprotein inhibitor INot AvailableNot Available
P-glycoprotein inhibitor IINot AvailableNot Available
Renal organic cation transporterNot AvailableNot Available
CYP450 2C9 substrateNot AvailableNot Available
CYP450 2D6 substrateNot AvailableNot Available
CYP450 3A4 substrateNot AvailableNot Available
CYP450 1A2 substrateNot AvailableNot Available
CYP450 2C9 inhibitorNot AvailableNot Available
CYP450 2D6 inhibitorNot AvailableNot Available
CYP450 2C19 inhibitorNot AvailableNot Available
CYP450 3A4 inhibitorNot AvailableNot Available
CYP450 inhibitory promiscuityNot AvailableNot Available
Ames testNot AvailableNot Available
CarcinogenicityNot AvailableNot Available
BiodegradationNot AvailableNot Available
Rat acute toxicityNot AvailableNot applicable
hERG inhibition (predictor I)Not AvailableNot Available
hERG inhibition (predictor II)Not AvailableNot Available
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Capsuleoral20 mg/1
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5856529 No1997-12-092017-12-09Us
US8785492 No2013-01-252033-01-25Us
US9060995 No2013-01-252033-01-25Us
USUS5856529 A No1997-12-092017-12-09Us
USUS8785492 B2 No2013-01-252033-01-25Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
boiling point442.553°CMSDS
water solubility1.1 mg/mLMSDS
logP2.43MSDS
Predicted Properties
PropertyValueSource
Water Solubility0.0216 mg/mLALOGPS
logP3.35ALOGPS
logP2.22ChemAxon
logS-4.1ALOGPS
pKa (Strongest Acidic)4.41ChemAxon
pKa (Strongest Basic)6.46ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area41.82 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity70.87 m3·mol-1ChemAxon
Polarizability27.91 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General References
  1. 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. [PubMed:25534555 ]
  2. 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. [PubMed:25685859 ]
  3. 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. [PubMed:25422900 ]
  4. 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. [PubMed:12661062 ]
External Links
ATC CodesN05CH03
AHFS Codes
  • 28:24.92
PDB EntriesNot Available
FDA labelDownload (249 KB)
MSDSDownload (203 KB)
Interactions
Drug Interactions
Drug
AbirateroneThe serum concentration of Tasimelteon can be increased when it is combined with Abiraterone.
AtazanavirThe serum concentration of Tasimelteon can be increased when it is combined with Atazanavir.
AzelastineTasimelteon may increase the central nervous system depressant (CNS depressant) activities of Azelastine.
BaclofenThe risk or severity of adverse effects can be increased when Baclofen is combined with Tasimelteon.
BexaroteneThe serum concentration of Tasimelteon can be decreased when it is combined with Bexarotene.
BoceprevirThe serum concentration of Tasimelteon can be increased when it is combined with Boceprevir.
BortezomibThe metabolism of Tasimelteon can be decreased when combined with Bortezomib.
BosentanThe serum concentration of Tasimelteon can be decreased when it is combined with Bosentan.
BrimonidineBrimonidine may increase the central nervous system depressant (CNS depressant) activities of Tasimelteon.
BuprenorphineTasimelteon may increase the central nervous system depressant (CNS depressant) activities of Buprenorphine.
CarbamazepineThe serum concentration of Tasimelteon can be decreased when it is combined with Carbamazepine.
CeritinibThe serum concentration of Tasimelteon can be increased when it is combined with Ceritinib.
CiprofloxacinThe serum concentration of Tasimelteon can be increased when it is combined with Ciprofloxacin.
ClarithromycinThe serum concentration of Tasimelteon can be increased when it is combined with Clarithromycin.
CobicistatThe serum concentration of Tasimelteon can be increased when it is combined with Cobicistat.
Cyproterone acetateThe serum concentration of Tasimelteon can be decreased when it is combined with Cyproterone acetate.
DabrafenibThe serum concentration of Tasimelteon can be decreased when it is combined with Dabrafenib.
DarunavirThe serum concentration of Tasimelteon can be increased when it is combined with Darunavir.
DeferasiroxThe serum concentration of Tasimelteon can be decreased when it is combined with Deferasirox.
DoxylamineDoxylamine may increase the central nervous system depressant (CNS depressant) activities of Tasimelteon.
DronabinolDronabinol may increase the central nervous system depressant (CNS depressant) activities of Tasimelteon.
DroperidolDroperidol may increase the central nervous system depressant (CNS depressant) activities of Tasimelteon.
EnzalutamideThe serum concentration of Tasimelteon can be decreased when it is combined with Enzalutamide.
EthanolTasimelteon may increase the central nervous system depressant (CNS depressant) activities of Ethanol.
FluvoxamineThe serum concentration of Tasimelteon can be increased when it is combined with Fluvoxamine.
FosphenytoinThe serum concentration of Tasimelteon can be decreased when it is combined with Fosphenytoin.
HydrocodoneTasimelteon may increase the central nervous system depressant (CNS depressant) activities of Hydrocodone.
HydroxyzineHydroxyzine may increase the central nervous system depressant (CNS depressant) activities of Tasimelteon.
IdelalisibThe serum concentration of Tasimelteon can be increased when it is combined with Idelalisib.
IndinavirThe serum concentration of Tasimelteon can be increased when it is combined with Indinavir.
ItraconazoleThe serum concentration of Tasimelteon can be increased when it is combined with Itraconazole.
KetoconazoleThe serum concentration of Tasimelteon can be increased when it is combined with Ketoconazole.
LorazepamThe risk or severity of adverse effects can be increased when Lorazepam is combined with Tasimelteon.
Magnesium SulfateMagnesium Sulfate may increase the central nervous system depressant (CNS depressant) activities of Tasimelteon.
MethotrimeprazineTasimelteon may increase the central nervous system depressant (CNS depressant) activities of Methotrimeprazine.
MethoxsalenThe serum concentration of Tasimelteon can be increased when it is combined with Methoxsalen.
MetyrosineTasimelteon may increase the sedative activities of Metyrosine.
MexiletineThe serum concentration of Tasimelteon can be increased when it is combined with Mexiletine.
MinocyclineMinocycline may increase the central nervous system depressant (CNS depressant) activities of Tasimelteon.
MirtazapineTasimelteon may increase the central nervous system depressant (CNS depressant) activities of Mirtazapine.
MitotaneThe serum concentration of Tasimelteon can be decreased when it is combined with Mitotane.
NabiloneNabilone may increase the central nervous system depressant (CNS depressant) activities of Tasimelteon.
NefazodoneThe serum concentration of Tasimelteon can be increased when it is combined with Nefazodone.
NelfinavirThe serum concentration of Tasimelteon can be increased when it is combined with Nelfinavir.
OfloxacinThe serum concentration of Tasimelteon can be increased when it is combined with Ofloxacin.
OrphenadrineTasimelteon may increase the central nervous system depressant (CNS depressant) activities of Orphenadrine.
ParaldehydeTasimelteon may increase the central nervous system depressant (CNS depressant) activities of Paraldehyde.
ParoxetineThe risk or severity of adverse effects can be increased when Tasimelteon is combined with Paroxetine.
Peginterferon alfa-2bThe serum concentration of Tasimelteon can be increased when it is combined with Peginterferon alfa-2b.
PerampanelPerampanel may increase the central nervous system depressant (CNS depressant) activities of Tasimelteon.
PhenobarbitalThe serum concentration of Tasimelteon can be decreased when it is combined with Phenobarbital.
PhenytoinThe serum concentration of Tasimelteon can be decreased when it is combined with Phenytoin.
PosaconazoleThe serum concentration of Tasimelteon can be increased when it is combined with Posaconazole.
PramipexoleTasimelteon may increase the sedative activities of Pramipexole.
PrimaquineThe serum concentration of Tasimelteon can be increased when it is combined with Primaquine.
PrimidoneThe serum concentration of Tasimelteon can be decreased when it is combined with Primidone.
RifabutinThe serum concentration of Tasimelteon can be decreased when it is combined with Rifabutin.
RifampicinThe serum concentration of Tasimelteon can be decreased when it is combined with Rifampicin.
RifapentineThe serum concentration of Tasimelteon can be decreased when it is combined with Rifapentine.
RitonavirThe serum concentration of Tasimelteon can be increased when it is combined with Ritonavir.
RopiniroleTasimelteon may increase the sedative activities of Ropinirole.
RotigotineTasimelteon may increase the sedative activities of Rotigotine.
RufinamideThe risk or severity of adverse effects can be increased when Rufinamide is combined with Tasimelteon.
SaquinavirThe serum concentration of Tasimelteon can be increased when it is combined with Saquinavir.
SiltuximabThe serum concentration of Tasimelteon can be decreased when it is combined with Siltuximab.
Sodium oxybateTasimelteon may increase the central nervous system depressant (CNS depressant) activities of Sodium oxybate.
St. John's WortThe serum concentration of Tasimelteon can be decreased when it is combined with St. John's Wort.
StiripentolThe serum concentration of Tasimelteon can be increased when it is combined with Stiripentol.
SuvorexantTasimelteon may increase the central nervous system depressant (CNS depressant) activities of Suvorexant.
TapentadolTapentadol may increase the central nervous system depressant (CNS depressant) activities of Tasimelteon.
TelaprevirThe serum concentration of Tasimelteon can be increased when it is combined with Telaprevir.
TelithromycinThe serum concentration of Tasimelteon can be increased when it is combined with Telithromycin.
TeriflunomideThe serum concentration of Tasimelteon can be decreased when it is combined with Teriflunomide.
ThalidomideTasimelteon may increase the central nervous system depressant (CNS depressant) activities of Thalidomide.
TocilizumabThe serum concentration of Tasimelteon can be decreased when it is combined with Tocilizumab.
VemurafenibThe serum concentration of Tasimelteon can be increased when it is combined with Vemurafenib.
VoriconazoleThe serum concentration of Tasimelteon can be increased when it is combined with Voriconazole.
ZolpidemTasimelteon may increase the central nervous system depressant (CNS depressant) activities of Zolpidem.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
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 inhibit adenylate cyclase activity.
Gene Name:
MTNR1A
Uniprot ID:
P48039
Molecular Weight:
39374.315 Da
References
  1. 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. [PubMed:25534555 ]
Kind
Protein
Organism
Human
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 inhibit adenylate cyclase activity.
Gene Name:
MTNR1B
Uniprot ID:
P49286
Molecular Weight:
40187.895 Da
References
  1. 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. [PubMed:25534555 ]
Comments
comments powered by Disqus
Drug created on May 14, 2015 10:07 / Updated on July 28, 2016 01:52