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{{Short description|Drug formerly under development for treatment of menopause symptoms}}
{{Drugbox
{{Drugbox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 455854971
| IUPAC_name = (''S'')-1,2,3,4,10,14b-hexahydro-2-methylpyrazino(2,1-a)pyrido(2,3-c)(2)benzazepine
| IUPAC_name = (''S'')-1,2,3,4,10,14b-hexahydro-2-methylpyrazino(2,1-a)pyrido(2,3-c)(2)benzazepine
| image = (S)-Mirtazapin Structural Formulae.png
| image = .
| width = 200

<!--Clinical data-->
<!--Clinical data-->
| tradename =
| tradename =
| pregnancy_category =
| pregnancy_category =
| legal_status = Uncontrolled
| legal_status = Uncontrolled
| routes_of_administration = [[Mouth|Oral]]
| routes_of_administration = [[|Oral]]

<!--Pharmacokinetic data-->
<!--Pharmacokinetic data-->
| bioavailability =
| bioavailability =
| metabolism = Liver ([[CYP2D6]])<ref name="urlwww.page-meeting.org">{{cite web | url = http://www.page-meeting.org/pdf_assets/2259-posterPAGE2008_SP.pdf | title = A population analysis on the effects of the CYP2D6 deficiency on pharmacokinetics and exposure of esmirtazapine in healthy volunteers}}</ref>
| metabolism = Liver ([[CYP2D6]])<ref name="urlwww.page-meeting.org">{{cite web | url = http://www.page-meeting.org/pdf_assets/2259-posterPAGE2008_SP.pdf | title = A population analysis on the effects of the CYP2D6 deficiency on pharmacokinetics and exposure of esmirtazapine in healthy volunteers}}</ref>
| elimination_half-life = 10 hours<ref name="insommnia">{{cite journal | vauthors = Ruwe F, IJzerman-Boon P, Roth T, Zammit G, Ivgy-May N | title = A Phase 2 Randomized Dose-Finding Study With Esmirtazapine in Patients With Primary Insomnia | journal = Journal of Clinical Psychopharmacology | volume = 36 | issue = 5 | pages = 457–464 | date = October 2016 | pmid = 27482970 | doi = 10.1097/JCP.0000000000000546 | s2cid = 25639396 }}</ref>
| elimination_half-life =
| excretion =
| excretion =

<!--Identifiers-->
<!--Identifiers-->
| index_label =
| index2_label = E. maleate
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 61337-87-9
| CAS_number = 61337-87-9
| ATC_prefix = none
| ATC_prefix = none
| ATC_suffix =
| ATC_suffix =
| PubChem = 6451144
| = 6451144
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 2342166
| ChemSpiderID = 2342166
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 4685R51V7M
| UNII = 4685R51V7M
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D04055
| KEGG = D04055
⚫
| PubChem = 3085218

| DrugBank_Ref = {{drugbankcite|changed|drugbank}}
| DrugBank = DB06678
<!--Chemical data-->
<!--Chemical data-->
| C=21 | H=23 | N=3 | O=4
| C= | H= | N=3
| smiles = CN1CCN2c3c(cccn3)Cc4ccccc4[C@H]2C1
| molecular_weight = 381.43 g/mol
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| smiles = CN1CCN2C(C1)C3=CC=CC=C3CC4=C2N=CC=C4
⚫
| StdInChI = 1S/C17H19N3/c1-19-9-10-20-16(12-19)15-7-3-2-5-13(15)11-14-6-4-8-18-17(14)20/h2-8,16H,9-12H2,1H3/t16-/m1/s1
⚫
| PubChem = 3085218
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| InChI = 1/C17H19N3/c1-19-9-10-20-16(12-19)15-7-3-2-5-13(15)11-14-6-4-8-18-17(14)20/h2-8,16H,9-12H2,1H3/t16-/m1/s1
| InChIKey = RONZAEMNMFQXRA-MRXNPFEDBJ
| = RONZAEMNMFQXRA-
⚫
| StdInChI = 1S/C17H19N3/c1-19-9-10-20-16(12-19)15-7-3-2-5-13(15)11-14-6-4-8-18-17(14)20/h2-8,16H,9-12H2,1H3/t16-/m1/s1
| StdInChIKey = RONZAEMNMFQXRA-MRXNPFEDSA-N
| melting_point = 114
| melting_point = 114
| melting_high = 116
| melting_high = 116
| solubility = Soluble in [[methanol]] and [[chloroform]]
| solubility = Soluble in [[methanol]] and [[chloroform]]
| sol_units = &nbsp;
}}
}}


'''Esmirtazapine''' ('''ORG-50,081''') is a [[drug]] which is under development by [[Organon International|Organon]] for the treatment of [[insomnia]] and [[vasomotor]] [[symptom]]s (e.g., [[hot flash]]es) associated with [[menopause]].<ref name="urlFuture Treatments for Depression, Anxiety, Sleep Disorders, Psychosis, and ADHD -- Neurotransmitter.net">{{cite web | url = http://www.neurotransmitter.net/newdrugs.html | title = Future Treatments for Depression, Anxiety, Sleep Disorders, Psychosis, and ADHD -- Neurotransmitter.net | work = | accessdate = }}</ref><ref name="urlA Long-Term Safety Study of Org 50081 in Elderly Outpatients With Chronic Primary Insomnia (176005)(P05697) - Full Text View - ClinicalTrials.gov">{{cite web | url = http://clinicaltrials.gov/ct2/show/NCT00561574 | title = A Long-Term Safety Study of Org 50081 in Elderly Outpatients With Chronic Primary Insomnia (176005)(P05697) - Full Text View - ClinicalTrials.gov | format = | work = | accessdate = }}</ref><ref name="pmid18673166">{{cite journal | author = Teegarden BR, Al Shamma H, Xiong Y | title = 5-HT(2A) inverse-agonists for the treatment of insomnia | journal = Current Topics in Medicinal Chemistry | volume = 8 | issue = 11 | pages = 969–76 | year = 2008 | pmid = 18673166 | doi = 10.2174/156802608784936700| url = }}</ref><ref name="pmid19775194">{{cite journal | author = Lewis V | title = Undertreatment of menopausal symptoms and novel options for comprehensive management | journal = Current Medical Research and Opinion | volume = 25 | issue = 11 | pages = 2689–98 | year = 2009 | month = November | pmid = 19775194 | doi = 10.1185/03007990903240519 | url = http://informahealthcare.com/doi/abs/10.1185/03007990903240519}}</ref> As of 2009 it is in [[phase III]] [[clinical trial]]s.<ref name="urlFuture Treatments for Depression, Anxiety, Sleep Disorders, Psychosis, and ADHD -- Neurotransmitter.net"/> Esmirtazapine is the (''S'')-(+)-[[enantiomer]] of [[mirtazapine]] and possesses similar overall [[pharmacology]], including [[inverse agonist]] actions at [[H1 receptor|H<sub>1</sub>]] and [[5-HT2 receptor|5-HT<sub>2</sub> receptor]]s and [[receptor antagonist|antagonist]] actions at [[alpha-2 adrenergic receptor|α<sub>2</sub>-adrenergic receptor]]s.<ref name="urlFuture Treatments for Depression, Anxiety, Sleep Disorders, Psychosis, and ADHD -- Neurotransmitter.net"/><ref name="isbn0-521-88663-5">{{cite book | author = | title = Depression and bipolar disorder: Stahl's essential psychopharmacology | publisher = Cambridge University Press | location = Cambridge, UK | year = 2008 | pages = | isbn = 0-521-88663-5 | oclc = | doi = | url = http://books.google.com/?id=zqvVZOea2JAC&lpg=PA112&dq=esmirtazapine&pg=PA112#v=onepage&q=&f=false}}</ref> As of March 2010, Merck terminated internal clinical development program for esmirtazapine, for hot flashes and insomnia, for strategic reasons.<ref>http://www.merck.com/investors/financials/form-10-K-2009-final.pdf</ref>
'''Esmirtazapine''' ('''ORG-50,081''') is a [[]] under development by [[Organon International|Organon]] for the treatment of [[insomnia]] and [[vasomotor]] [[symptom]]s (e.g., [[hot flash]]es) associated with [[menopause]].<ref name="urlFuture Treatments for Depression, Anxiety, Sleep Disorders, Psychosis, and ADHD -- Neurotransmitter.net">{{cite web | url = http://www.neurotransmitter.net/newdrugs.html | title = Future Treatments for Depression, Anxiety, Sleep Disorders, Psychosis, and ADHD | work = }}</ref><ref name="">{{|NCT00561574|A Long-Term Safety Study of Org 50081 in Elderly Outpatients With Chronic Primary Insomnia (176005)}}</ref><ref name="pmid18673166">{{cite journal | = Teegarden BR, Al Shamma H, Xiong Y | title = 5-HT(2A) inverse-agonists for the treatment of insomnia | journal = Current Topics in Medicinal Chemistry | volume = 8 | issue = 11 | pages = | year = 2008 | pmid = 18673166 | doi = 10.2174/156802608784936700 }}</ref><ref name="pmid19775194">{{cite journal | = Lewis V | title = Undertreatment of menopausal symptoms and novel options for comprehensive management | journal = Current Medical Research and Opinion | volume = 25 | issue = 11 | pages = | = 2009 | pmid = 19775194 | doi = 10.1185/03007990903240519 | = }}</ref> Esmirtazapine is the (''S'')-(+)-[[enantiomer]] of [[mirtazapine]] and possesses similar overall [[pharmacology]], including [[inverse agonist]] actions at [[H1 receptor|H<sub>1</sub>]] and [[5-HT2 receptor|5-HT<sub>2</sub> receptor]]s and [[receptor antagonist|antagonist]] actions at [[alpha-2 adrenergic receptor|α<sub>2</sub>-adrenergic receptor]]s.<ref name="urlFuture Treatments for Depression, Anxiety, Sleep Disorders, Psychosis, and ADHD -- Neurotransmitter.net"/><ref name="isbn0-521-88663-5">{{cite book | = | title = Depression and bipolar disorder: Stahl's essential psychopharmacology | publisher = Cambridge University Press | location = Cambridge, UK | year = 2008 | isbn = 0-521-88663-5 | url = ://books.google.com/?id=zqvVZOea2JAC&=esmirtazapine&pg=PA112}}</ref>

Notably, esmirtazapine has a shorter half life of around 10&nbsp;hours, compared to R-mirtazapine and racemic mixture, which has a half-life of 18–40&nbsp;hours.<ref name="insommnia"/> Merck has run several studies on low dose (3–4.5&nbsp;mg) esmirtazapine for the treatment of insomnia. It is attractive for treating insomnia since it is a potent H<sub>1</sub>-inhibitor and a 5-HT<sub>2A</sub> antagonist.<ref>{{cite journal | vauthors = Ivgy-May N, Ruwe F, Krystal A, Roth T | title = Esmirtazapine in non-elderly adult patients with primary insomnia: efficacy and safety from a randomized, 6-week sleep laboratory trial | journal = Sleep Medicine | volume = 16 | issue = 7 | pages = 838–844 | date = July 2015 | pmid = 26047892 | doi = 10.1016/j.sleep.2015.04.001 }}</ref><ref name="insommnia"/> Unlike low-dose mirtazapine, the half life (10&nbsp;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).<ref>{{cite journal | vauthors = Ivgy-May N, Hajak G, van Osta G, Braat S, Chang Q, Roth T | title = Efficacy and safety of esmirtazapine in adult outpatients with chronic primary insomnia: a randomized, double-blind placebo-controlled study and open-label extension | journal = Journal of Clinical Sleep Medicine | volume = 16 | issue = 9 | pages = 1455–1467 | date = September 2020 | pmid = 32351205 | pmc = 7970588 | doi = 10.5664/jcsm.8526 }}</ref>

In March 2010, Merck terminated its internal clinical development program for esmirtazapine for hot flashes and insomnia, "for strategic reasons".<ref>{{Cite web |url=http://www.merck.com/investors/financials/form-10-K-2009-final.pdf |title=Form 10-K | publisher = Merck & Co., Inc. |access-date=2011-05-03 |archive-date=2011-08-05 |archive-url=https://web.archive.org/web/20110805215529/http://www.merck.com/investors/financials/form-10-K-2009-final.pdf |url-status=dead }}</ref>


== See also ==
== See also ==
* [[Mirtazapine]]
* [[]]


== References ==
== References ==
{{Reflist}}
{{Reflist}}


== External links ==
*{{Commons category-inline}}

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