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Title: Tasimelteon  
Author: World Heritage Encyclopedia
Language: English
Subject: Melatonin receptor agonist, Insomnia, Melatonin receptor, Z-drug, Suvorexant
Collection: Benzofurans, Cyclopropanes, Melatonin Receptor Agonists, Propionamides, Sedatives
Publisher: World Heritage Encyclopedia


Systematic (IUPAC) name
(1R, 2R)-N-[2-(2,3-dihydrobenzofuran-4-yl)cyclopropylmethyl]propanamide
Clinical data
Trade names Hetlioz
Pregnancy cat.
Legal status
Routes Oral
Pharmacokinetic data
Bioavailability not determined in humans[1]
Protein binding 89–90%
Metabolism extensive hepatic, primarily CYP1A2 and CYP3A4-mediated
Half-life 0.9–1.7 h / 0.8–5.9 h (terminal)
Excretion 80% in urine, 4% in feces
CAS number  YesY
ATC code None
ChemSpider  N
Chemical data
Formula C15H19NO2 
Mol. mass 245.32 g/mol

Tasimelteon (trade name Hetlioz) is a drug approved by the FDA[2] solely for the treatment of non-24-hour sleep–wake disorder (often designated as N24HSWD).[3] It is a selective agonist for the melatonin receptors MT1 and MT2 in the suprachiasmatic nucleus of the brain, similar to other members of the melatonin receptor agonist class of which ramelteon (2005) and agomelatine (2009) were the first approved.[4] In June 2014, the European Medicines Agency accepted an EU filing application for tasimelteon.[5] As a treatment for N24HSWD, as with melatonin or other melatonin derivatives, the patient typically experiences improved sleep quality while taking the drug, but reverts to baseline sleep performance within a month of discontinuation.[6]


  • Development 1
  • FDA approval 2
  • Toxicity 3
  • See also 4
  • References 5


Tasimelteon (previously known as BMS-214,778) was developed for the treatment of insomnia and other sleep disorders. A phase II trial on circadian rhythm sleep disorders was concluded in March 2005.[7] A phase III insomnia trial was conducted in 2006.[8] A second phase III trial on insomnia, this time concerning primary insomnia, was completed in June 2008.[9] In 2010, the FDA granted orphan drug status to tasimelteon, then regarded as an investigational medication, for use in totally blind adults with N24HSWD.[10] This status encourages development of drugs for rare conditions that might otherwise lack sufficient profit motive through mechanisms such as easing the approval process and extending exclusivity periods.

On completion of Phase III trials, interpretations of the clinical trials by the researchers concluded that the drug may have therapeutic potential for transient insomnia in circadian rhythm sleep disorders.[11] Adam Feuerstein writing for The Street in June 2013 raised significant concerns over the objectivity of the study endpoints, citing relaxed participant screening and moving goalposts.[12] A year-long (2011–2012) study at Harvard tested the use of tasimelteon in blind subjects with non-24-hour sleep–wake disorder. The drug has not been tested in children.

FDA approval

In May 2013 Vanda Pharmaceuticals submitted a New Drug Application to the Food and Drug Administration for tasimelteon for the treatment of non-24-hour sleep–wake disorder in totally blind people. It was approved by the FDA on January 31, 2014 under the brand name Hetlioz.[3]


Experiments with rodents revealed fertility impairments, an increase in certain cancers, and serious adverse events during pregnancy at dosages in excess of what is considered the "human dose".[13][14]

See also


  1. ^ "Tasimelteon Advisory Committee Meeting Briefing Materials". Vanda Pharmaceuticals Inc. November 2013. 
  2. ^ "FDA transcript approval minutes". FDA. November 14, 2013. 
  3. ^ a b Food and Drug Administration (January 31, 2014). "FDA approves Hetlioz: first treatment for non-24 hour sleep-wake disorder". FDA. 
  4. ^ Vachharajani, Nimish N., Yeleswaram, Krishnaswamy, Boulton, David W. (April 2003). "Preclinical pharmacokinetics and metabolism of BMS-214778, a novel melatonin receptor agonist". Journal of Pharmaceutical Sciences 92 (4): 760–72.  
  5. ^ "tasimelteon (Hetlioz) UKMi New Drugs Online Database". Retrieved August 6, 2014. 
  6. ^ Sack, R. L.; Brandes, R. W.; Kendall, A. R.; Lewy, A. J. (2000). "Entrainment of Free-Running Circadian Rhythms by Melatonin in Blind People". New England Journal of Medicine 343 (15): 1070–7.  
  7. ^ "Safety and Efficacy of VEC-162 on Circadian Rhythm in Healthy Adult Volunteers".  |accessdate=May 15, 2014
  8. ^ "VEC-162 Study in Healthy Adult Volunteers in a Model of Insomnia". Retrieved May 15, 2014. 
  9. ^ "VEC-162 Study in Adult Patients With Primary Insomnia". Retrieved May 15, 2014. 
  10. ^ Lynne Lamberg. "Improving Sleep and Alertness in the Blind (Part 5)". Matilda Ziegler Magazine for the Blind. Retrieved May 15, 2014. 
  11. ^ Shantha MW Rajaratnam, Mihael H Polymeropoulos, Dennis M Fisher, Thomas Roth, Christin Scott, Gunther Birznieks, Elizabeth B Klerman (2009-02-07). "Melatonin agonist tasimelteon (VEC-162) for transient insomnia after sleep-time shift: two randomised controlled multicentre trials". The Lancet 373 (9662): 482–491.  
  12. ^ Adam Feuerstein (June 19, 2013). "Vanda's Sleep Disorder Drug Is A Nightmare". The Street. Retrieved May 15, 2014. 'Less than 5% of individuals matched the traditional textbook definition of N24HSWD with a clearly non-24 hour sleep period,' Vanda states in a scientific poster presented in June 2012 which characterized patients screened for entry into the phase III study. 
  13. ^ "Side Effects Drug Center: Hetlioz Clinical Pharmacology". RxList. February 10, 2014. 
  14. ^ "Side Effects Drug Center: Hetlioz Warnings and Precautions". RxList. February 10, 2014. 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. 
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