Chemistry:Esmirtazapine

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Short description: Drug formerly under development for treatment of menopause symptoms
Esmirtazapine
Esmirtazapine 2D structure.svg
Clinical data
Routes of
administration		Oral
ATC code
  • none
Legal status
Legal status
  • In general: uncontrolled
Pharmacokinetic data
MetabolismLiver (CYP2D6)[2]
Elimination half-life10 hours[1]
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
Chemical and physical data
FormulaC17H19N3
Molar mass265.360 g·mol−1
3D model (JSmol)
Melting point114 to 116 °C (237 to 241 °F)
Solubility in waterSoluble in methanol and chloroform 
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Esmirtazapine (ORG-50,081) is a tetracyclic antidepressant drug that was under development by Organon for the treatment of insomnia and vasomotor symptoms (e.g., hot flashes) associated with menopause.[3][4][5][6] Esmirtazapine is the (S)-(+)-enantiomer of mirtazapine and possesses similar overall pharmacology, including inverse agonist actions at H1 and 5-HT2 receptors and antagonist actions at α2-adrenergic receptors.[3][7]

Notably, esmirtazapine has a shorter half life of around 10 hours, compared to R-mirtazapine and racemic mixture, which has a half-life of 18–40 hours.[1] Merck has run several studies on low dose (3–4.5 mg) esmirtazapine for the treatment of insomnia. It is attractive for treating insomnia since it is a potent H1-inhibitor and a 5-HT2A antagonist.[8][1] Unlike low-dose mirtazapine, the half life (10 hours) is short enough that next-day sedation may be manageable, however, for people with CYP2D6 polymorphisms, which constitute a sizable fraction of the population, the half-life is expected to be quite a bit longer. Merck researchers claimed that the incidence of next-day sedation was not a problem in one of their studies, but this claim has been challenged (15% of patients complained of daytime sleepiness vs 3.5% in the placebo group).[9]

In March 2010, Merck terminated its internal clinical development program for esmirtazapine for hot flashes and insomnia, "for strategic reasons".[10]

See also

References

  1. ↑ 1.0 1.1 1.2 "A Phase 2 Randomized Dose-Finding Study With Esmirtazapine in Patients With Primary Insomnia". Journal of Clinical Psychopharmacology 36 (5): 457–464. October 2016. doi:10.1097/JCP.0000000000000546. PMID 27482970. 
  2. ↑ "A population analysis on the effects of the CYP2D6 deficiency on pharmacokinetics and exposure of esmirtazapine in healthy volunteers". Oss, The Netherlands: Schering-Plough Corporation. http://www.page-meeting.org/pdf_assets/2259-posterPAGE2008_SP.pdf. 
  3. ↑ 3.0 3.1 "Future Treatments for Depression, Anxiety, Sleep Disorders, Psychosis, and ADHD". Neurotransmitter.net. http://www.neurotransmitter.net/newdrugs.html. 
  4. ↑ Clinical trial number NCT00561574 for "A Long-Term Safety Study of Org 50081 in Elderly Outpatients With Chronic Primary Insomnia (176005)" at ClinicalTrials.gov
  5. ↑ "5-HT(2A) inverse-agonists for the treatment of insomnia". Current Topics in Medicinal Chemistry 8 (11): 969–976. 2008. doi:10.2174/156802608784936700. PMID 18673166. 
  6. ↑ "Undertreatment of menopausal symptoms and novel options for comprehensive management". Current Medical Research and Opinion 25 (11): 2689–2698. November 2009. doi:10.1185/03007990903240519. PMID 19775194. 
  7. ↑ "Antidepresents". Depression and bipolar disorder: Stahl's essential psychopharmacology (3rd ed.). Cambridge, UK: Cambridge University Press. 2008. ISBN 978-0-521-88663-5. https://books.google.com/books?id=zqvVZOea2JAC&q=esmirtazapine&pg=PA112. 
  8. ↑ "Esmirtazapine in non-elderly adult patients with primary insomnia: efficacy and safety from a randomized, 6-week sleep laboratory trial". Sleep Medicine 16 (7): 838–844. July 2015. doi:10.1016/j.sleep.2015.04.001. PMID 26047892. 
  9. ↑ "Efficacy and safety of esmirtazapine in adult outpatients with chronic primary insomnia: a randomized, double-blind placebo-controlled study and open-label extension". Journal of Clinical Sleep Medicine 16 (9): 1455–1467. September 2020. doi:10.5664/jcsm.8526. PMID 32351205. 
  10. ↑ "Form 10-K". Merck & Co., Inc.. http://www.merck.com/investors/financials/form-10-K-2009-final.pdf. 

External links



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