Filorexant

Last updated
Filorexant
Filorexant.svg
Clinical data
Other namesMK-6096; MK6096
Routes of
administration 		By mouth
Drug class Orexin antagonist
ATC code
  • None
Pharmacokinetic data
Elimination half-life 3–6 hours [1]
Identifiers
  • [(2R,5R)-5-{[(5-Fluoro-2-pyridinyl)oxy]methyl}-2-methyl-1-piperidinyl][5-methyl-2-(2-pyrimidinyl)phenyl]methanone
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
PDB ligand
CompTox Dashboard (EPA)
ECHA InfoCard 100.203.042 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C24H25FN4O2
Molar mass 420.488 g·mol−1
3D model (JSmol)
  • C[C@@H]1CC[C@H](CN1C(=O)C2=C(C=CC(=C2)C)C3=NC=CC=N3)COC4=NC=C(C=C4)F
  • InChI=1S/C24H25FN4O2/c1-16-4-8-20(23-26-10-3-11-27-23)21(12-16)24(30)29-14-18(6-5-17(29)2)15-31-22-9-7-19(25)13-28-22/h3-4,7-13,17-18H,5-6,14-15H2,1-2H3/t17-,18-/m1/s1
  • Key:NPFDWHQSDBWQLH-QZTJIDSGSA-N

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, 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]

Contents

See also

Related Research Articles

<span class="mw-page-title-main">Orexin</span> Neuropeptide that regulates arousal, wakefulness, and appetite.

Orexin, also known as hypocretin, is a neuropeptide that regulates arousal, wakefulness, and appetite. It exists in the forms of orexin-A and orexin-B. The most common form of narcolepsy, type 1, in which the individual experiences brief losses of muscle tone, is caused by a lack of orexin in the brain due to destruction of the cells that produce it.

<span class="mw-page-title-main">SB-649868</span> Chemical compound

SB-649868 is a dual orexin receptor antagonist that was being developed by GlaxoSmithKline as a treatment for insomnia.

The orexin receptor (also referred to as the hypocretin receptor) is a G-protein-coupled receptor that binds the neuropeptide orexin. There are two variants, OX1 and OX2, each encoded by a different gene (HCRTR1, HCRTR2).

<span class="mw-page-title-main">Hypocretin (orexin) receptor 1</span> Protein-coding gene in the species Homo sapiens

Orexin receptor type 1 (Ox1R or OX1), also known as hypocretin receptor type 1 (HcrtR1), is a protein that in humans is encoded by the HCRTR1 gene.

<span class="mw-page-title-main">Hypocretin (orexin) receptor 2</span> Protein-coding gene in the species Homo sapiens

Orexin receptor type 2 (Ox2R or OX2), also known as hypocretin receptor type 2 (HcrtR2), is a protein that in humans is encoded by the HCRTR2 gene. It should not be confused for the protein CD200R1 which shares the alias OX2R but is a distinct, unrelated gene located on the human chromosome 3.

<span class="mw-page-title-main">Almorexant</span> Orexin antagonist compound

Almorexant (INN), also known by its development code ACT-078573, is an orexin antagonist, acting as a competitive antagonist of the OX1 and OX2 orexin receptors, which was being developed by the pharmaceutical companies Actelion and GSK for the treatment of insomnia. Development of the drug was abandoned in January 2011 due to concerns over the hepatic safety of almorexant after transient increases in liver enzymes were observed in trials.

<span class="mw-page-title-main">Telcagepant</span> Chemical compound

Telcagepant (INN) is a calcitonin gene-related peptide receptor antagonist which was an investigational drug for the acute treatment and prevention of migraine, developed by Merck & Co.

<span class="mw-page-title-main">SB-334867</span> Chemical compound

SB-334867 is an orexin antagonist. It was the first non-peptide antagonist developed that is selective for the orexin receptor subtype OX1, with around 50x selectivity for OX1 over OX2 receptors. It has been shown to produce sedative and anorectic effects in animals, and has been useful in characterising the orexinergic regulation of brain systems involved with appetite and sleep, as well as other physiological processes. The hydrochloride salt of SB-334867 has been demonstrated to be hydrolytically unstable, both in solution and as the solid. Orexin antagonists have multiple potential clinical applications including the treatment of drug addiction, insomnia, obesity and diabetes.

<span class="mw-page-title-main">Suvorexant</span> Medication used to treat insomnia

Suvorexant, sold under the brand name Belsomra, is an orexin antagonist medication which is used in the treatment of insomnia. It is indicated specifically for the treatment of insomnia characterized by difficulties with sleep onset and/or maintenance in adults. Suvorexant helps with falling asleep faster, sleeping longer, being awake less in the middle of the night, and having better quality of sleep. Its effectiveness is modest, and is similar to that of other orexin antagonists, but is lower than that of benzodiazepines and Z-drugs. Suvorexant is taken by mouth.

An orexin receptor antagonist, or orexin antagonist, is a drug that inhibits the effect of orexin by acting as a receptor antagonist of one (selective orexin receptor antagonist or SORA) or both (dual orexin receptor antagonis or DORA) of the orexin receptors, OX1 and OX2. Medical applications include treatment of sleep disorders such as insomnia.

Calcitonin gene-related peptide (CGRP) receptor antagonists are a class of drugs that act as antagonists of the calcitonin gene-related peptide receptor (CGRPR).

<span class="mw-page-title-main">Seltorexant</span> Experimental anti-insomnia drug

Seltorexant, also known by its developmental code names MIN-202 and JNJ-42847922, is an orexin antagonist medication which is under development for the treatment of depression and insomnia. It is a selective antagonist of the orexin OX2 receptor (2-SORA). The medication is taken by mouth.

<span class="mw-page-title-main">Lemborexant</span> Chemical compound

Lemborexant, sold under the brand name Dayvigo, is an orexin antagonist medication which is used in the treatment of insomnia. It is indicated specifically for the treatment of insomnia characterized by difficulties with sleep onset and/or maintenance in adults. The medication is taken by mouth.

<span class="mw-page-title-main">Daridorexant</span> Medication used to treat insomnia

Daridorexant, sold under the brand name Quviviq, is an orexin antagonist medication which is used for the treatment of insomnia. Daridorexant is taken by mouth.

<span class="mw-page-title-main">Danavorexton</span> Chemical compound

Danavorexton is a selective orexin 2 receptor agonist. It is a small-molecule compound and is administered intravenously. The compound was found to dose-dependently produce wakefulness to a similar degree as modafinil in a phase 1 clinical trial. As of March 2021, danavorexton is under development for the treatment of narcolepsy, idiopathic hypersomnia, and sleep apnea. It is related to another orexin receptor agonist, firazorexton (TAK-994), the development of which was discontinued for safety reasons in October 2021.

<span class="mw-page-title-main">Vornorexant</span> Chemical compound

Vornorexant, also known by its developmental code names ORN-0829 and TS-142, is an orexin antagonist medication which is under development for the treatment of insomnia and sleep apnea. It is a dual orexin OX1 and OX2 receptor antagonist (DORA). The medication is taken by mouth. As of June 2021, vornorexant is in phase 2 clinical trials for insomnia and phase 1 trials for sleep apnea. It is under development by Taisho Pharmaceutical.

<span class="mw-page-title-main">Firazorexton</span> Chemical compound

Firazorexton (INNTooltip International Nonproprietary Name; development code TAK-994) is an experimental orexin 2 (OX2) receptor agonist first described in a 2019 patent filed by Takeda Pharmaceutical Company.

<span class="mw-page-title-main">ACT-539313</span> Chemical compound

ACT-539313 is an orexin antagonist medication which is under development for the treatment of binge eating disorder and was previously under development for the treatment of anxiety disorders. It is an orally active small-molecule compound with an elimination half-life of 3.3 to 6.5 hours and acts as a selective orexin OX1 receptor antagonist (1-SORA). As of May 2022, the drug is in phase 2 clinical trials for binge eating disorder. Following negative efficacy results of a phase 2 trial of ACT-539313 for binge eating disorder, Idorsia (the developer of ACT-539313) signaled in May 2022 that it would not pursue further development of the drug for this indication.

<span class="mw-page-title-main">Tebideutorexant</span> Chemical compound

Tebideutorexant (developmental code names JNJ-61393215, JNJ-3215) is an orexin antagonist medication which is under development for the treatment of depression and anxiety disorders. It is an orally active compound and acts as a selective antagonist of the orexin OX1 receptor (1-SORA). Preliminary clinical findings suggest that tebideutorexant may have anti-panic effects in humans. As of June 2023, tebideutorexant is in phase 2 clinical trials for the treatment of major depressive disorder while no further development has been reported for treatment of panic disorder and other anxiety disorders. The drug was originated and developed by Janssen Pharmaceuticals.

References

  1. 1 2 3 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.
  2. 1 2 "Filorexant". AdisInsight. Springer Nature Switzerland AG.
  3. ↑ 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.
  4. ↑ 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.
  5. ↑ 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.
  6. 1 2 3 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.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ 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.
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ 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.
  14. ↑ "Merck Pipeline". Merck. 2015. Retrieved 2015-05-14.


This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.