From Wikipedia, the free encyclopedia
Chemical compound
Filorexant (
INN Tooltip International Nonproprietary Name ,
USAN Tooltip United States Approved Name ; developmental code name MK-6096 ) is an
orexin antagonist which was under development by
Merck for the treatment of
insomnia ,
depression ,
diabetic neuropathy , and
migraine .
[2]
[3] It is a dual
antagonist of the
orexin
OX1 and
OX2 receptors .
[4]
[5] It has a relatively short
elimination half-life of 3 to 6 hours.
[1] However, it dissociates slowly from the orexin receptors and may thereby have a longer
duration .
[6] Possibly in relation to this, filorexant shows next-day
somnolence similarly to suvorexant.
[6] In
phase 2
clinical trials , filorexant was found to be effective in the treatment of insomnia,
[7] but was not effective in the treatment of
major depressive disorder ,
[8]
[9]
[10]
painful diabetic neuropathy ,
[11]
[12] or migraine.
[13] As of May 2015
[update] , filorexant was no longer listed on
Merck 's online development pipeline and hence development of the drug appears to have been discontinued.
[14]
[1]
[2] Development of filorexant may have been discontinued due to lack of differentiation from suvorexant (which was also developed by Merck).
[6]
See also
References
^
a
b
c Hoyer D, Jacobson LH (13 November 2017). "Orexin Receptor Antagonists". Current Sleep Medicine Reports . 3 (4): 342–353.
doi :
10.1007/s40675-017-0099-7 .
eISSN
2198-6401 .
hdl :
11343/282828 .
S2CID
80067706 .
^
a
b
"Filorexant" . AdisInsight . Springer Nature Switzerland AG.
^ Hoyer D, Jacobson LH (December 2013). "Orexin in sleep, addiction and more: is the perfect insomnia drug at hand?". Neuropeptides . 47 (6): 477–488.
doi :
10.1016/j.npep.2013.10.009 .
PMID
24215799 .
S2CID
6402764 .
^ Winrow CJ, Gotter AL, Cox CD, Tannenbaum PL, Garson SL, Doran SM, et al. (February 2012). "Pharmacological characterization of MK-6096 - a dual orexin receptor antagonist for insomnia". Neuropharmacology . 62 (2): 978–987.
doi :
10.1016/j.neuropharm.2011.10.003 .
PMID
22019562 .
S2CID
35304627 .
^ Peroutka SJ (January 2014). "Clinical trials update. 2013: year in review". Headache . 54 (1): 189–194.
doi :
10.1111/head.12267 .
PMID
24400767 .
S2CID
28141555 .
^
a
b
c Jacobson LH, Hoyer D, de Lecea L (May 2022). "Hypocretins (orexins): The ultimate translational neuropeptides". Journal of Internal Medicine . 291 (5): 533–556.
doi :
10.1111/joim.13406 .
PMID
35043499 .
S2CID
248119793 .
^ Connor KM, Mahoney E, Jackson S, Hutzelmann J, Zhao X, Jia N, et al. (August 2016).
"A Phase II Dose-Ranging Study Evaluating the Efficacy and Safety of the Orexin Receptor Antagonist Filorexant (MK-6096) in Patients with Primary Insomnia" . The International Journal of Neuropsychopharmacology . 19 (8): pyw022.
doi :
10.1093/ijnp/pyw022 .
PMC
5006195 .
PMID
26979830 .
^ Summers CH, Yaeger JD, Staton CD, Arendt DH, Summers TR (March 2020).
"Orexin/hypocretin receptor modulation of anxiolytic and antidepressive responses during social stress and decision-making: Potential for therapy" . Brain Research . 1731 : 146085.
doi :
10.1016/j.brainres.2018.12.036 .
PMC
6591110 .
PMID
30590027 .
^ Han Y, Yuan K, Zheng Y, Lu L (April 2020).
"Orexin Receptor Antagonists as Emerging Treatments for Psychiatric Disorders" . Neuroscience Bulletin . 36 (4): 432–448.
doi :
10.1007/s12264-019-00447-9 .
PMC
7142186 .
PMID
31782044 .
^ Connor KM, Ceesay P, Hutzelmann J, Snavely D, Krystal AD, Trivedi MH, et al. (August 2017).
"Phase II Proof-of-Concept Trial of the Orexin Receptor Antagonist Filorexant (MK-6096) in Patients with Major Depressive Disorder" . The International Journal of Neuropsychopharmacology . 20 (8): 613–618.
doi :
10.1093/ijnp/pyx033 .
PMC
5570043 .
PMID
28582570 .
^ Steiner MA, Winrow CJ (11 November 2014).
Insomnia and beyond - Exploring the therapeutic potential of orexin receptor antagonists . Frontiers E-books. pp. 3–.
ISBN
978-2-88919-330-1 .
^ Joseph Herring W, Ge JY, Jackson S, Assaid C, Connor KM, Michelson D (January 2018). "Orexin Receptor Antagonism in Painful Diabetic Neuropathy: A Phase 2 Trial With Filorexant". The Clinical Journal of Pain . 34 (1): 37–43.
doi :
10.1097/AJP.0000000000000503 .
PMID
28448426 .
S2CID
23060776 .
^ Chabi A, Zhang Y, Jackson S, Cady R, Lines C, Herring WJ, et al. (April 2015). "Randomized controlled trial of the orexin receptor antagonist filorexant for migraine prophylaxis". Cephalalgia . 35 (5): 379–388.
doi :
10.1177/0333102414544979 .
PMID
25106663 .
S2CID
20872932 .
^
"Merck Pipeline" . Merck. 2015. Retrieved 2015-05-14 .
External links