Suvorexant

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Suvorexant
MK4305 structure.png
Systematic (IUPAC) name
[(7R)-4-(5-chloro-1,3-benzoxazol-2-yl)-7-methyl-1,4-diazepan-1-yl][5-methyl-2-(2H-1,2,3-triazol-2-yl)phenyl]methanone
Clinical data
Legal status Investigational
Identifiers
CAS number 1030377-33-3 N
ATC code None
PubChem CID 24965990
ChemSpider 24662178 N
Chemical data
Formula C23H23ClN6O2 
Mol. mass 450.920 g/mol (free base)
 N (what is this?)  (verify)

Suvorexant (MK-4305) is a dual orexin receptor antagonist in development by Merck & Co. for the treatment of insomnia.[1][2][3] It is not currently approved for commercial use, but it has completed three Phase III trials.[4] Results look promising.[5] The recent FDA review showed that the drug is associated with increased somnolence the next day and users of higher doses had an increased rate of suicidal ideation.[6]

Suvorexant works by turning off wakefulness rather than by inducing sleep.[7]

Suvorexant looks set to reach the market, as the FDA's peripheral and central nervous system advisory committee reportedly agreed that the drug was generally safe and effective for treating sleep maintenance and latency. The current debate is over what dose should be recommended to patients.[8]

In the United States, the DEA has proposed placing Suvorexant into the list of schedule IV controlled substances. [9]

References[edit]

  1. ^ Cox, C. D.; Breslin, M. J.; Whitman, D. B.; Schreier, J. D.; McGaughey, G. B.; Bogusky, M. J.; Roecker, A. J.; Mercer, S. P.; Bednar, R. A.; Lemaire, W.; Bruno, J. G.; Reiss, D. R.; Harrell, C. M.; Murphy, K. L.; Garson, S. L.; Doran, S. M.; Prueksaritanont, T.; Anderson, W. B.; Tang, C.; Roller, S.; Cabalu, T. D.; Cui, D.; Hartman, G. D.; Young, S. D.; Koblan, K. S.; Winrow, C. J.; Renger, J. J.; Coleman, P. J. (2010). "Discovery of the Dual Orexin Receptor Antagonist [(7R)-4-(5-Chloro-1,3-benzoxazol-2-yl)-7-methyl-1,4-diazepan-1-yl][5-methyl-2-(2H-1,2,3-triazol-2-yl)phenyl]methanone (MK-4305) for the Treatment of Insomnia". Journal of Medicinal Chemistry 53 (14): 5320–5332. doi:10.1021/jm100541c. PMID 20565075.  edit
  2. ^ Baxter, C. A.; Cleator, E.; Brands, K. M. J.; Edwards, J. S.; Reamer, R. A.; Sheen, F. J.; Stewart, G. W.; Strotman, N. A.; Wallace, D. J. (2011). "The First Large-Scale Synthesis of MK-4305: A Dual Orexin Receptor Antagonist for the Treatment of Sleep Disorder". Organic Process Research & Development 15 (2): 367–375. doi:10.1021/op1002853.  edit
  3. ^ Winrow, C. J.; Gotter, A. L.; Cox, C. D.; Doran, S. M.; Tannenbaum, P. L.; Breslin, M. J.; Garson, S. L.; Fox, S. V.; Harrell, C. M.; Stevens, J.; Reiss, D. R.; Cui, D.; Coleman, P. J.; Renger, J. J. (2011). "Promotion of Sleep by Suvorexant—A Novel Dual Orexin Receptor Antagonist". Journal of Neurogenetics 25 (1–2): 52–61. doi:10.3109/01677063.2011.566953. PMID 21473737.  edit
  4. ^ Three completed trials:
  5. ^ Mieda, M; Sakurai, T (February 2013). "Orexin (hypocretin) receptor agonists and antagonists for treatment of sleep disorders. Rationale for development and current status.". CNS drugs 27 (2): 83–90. doi:10.1007/s40263-012-0036-8. PMID 23359095. 
  6. ^ "FDA has safety concerns about insomnia drug". USA Today. May 20, 2013. 
  7. ^ Kahn, Howie (June 1, 2012). "Sleep Better". In Koerth-Baker, Maggie. 32 Innovations That Will Change Your Tomorrow (New York Times). Retrieved November 29, 2012. 
  8. ^ http://www.rttnews.com/2123549/fda-panel-backs-merck-insomnia-drug-suvorexant-but-at-lower-doses.aspx
  9. ^ https://www.federalregister.gov/articles/2014/02/13/2014-03124/schedules-of-controlled-substances-placement-of-suvorexant-into-schedule-iv