Identification

Name
Esmirtazapine
Accession Number
DB06678
Type
Small Molecule
Groups
Investigational
Description

Esmirtazapine (SCH 900265) is a drug which was under development by Organon for the treatment of insomnia and vasomotor symptoms (e.g., hot flashes) associated with menopause. 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. Merck has terminated its internal clinical development program for esmirtazapine as of March 2010.

Structure
Thumb
Synonyms
  • (S)-1,2,3,4,10,14b-hexahydro-2-methylpyrazino(2,1-a)pyrido(2,3-c)(2)benzazepine
External IDs
ORG-44-20 / ORG-4420 / ORG-50,081 / SCH 900265
Product Ingredients
IngredientUNIICASInChI Key
Esmirtazapine hydrochlorideJ12BQ47O1N1448014-35-4SISMRXGXKXMBKT-PKLMIRHRSA-N
Esmirtazapine maleateI2U18E6JKA680993-85-5RPUBHMMISKEXSR-MLCLTIQSSA-N
Categories
UNII
4685R51V7M
CAS number
61337-87-9
Weight
Average: 265.36
Monoisotopic: 265.157897624
Chemical Formula
C17H19N3
InChI Key
RONZAEMNMFQXRA-MRXNPFEDSA-N
InChI
InChI=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
IUPAC Name
(7S)-5-methyl-2,5,19-triazatetracyclo[13.4.0.0²,⁷.0⁸,¹³]nonadeca-1(15),8,10,12,16,18-hexaene
SMILES
[H][C@]12CN(C)CCN1C1=C(CC3=CC=CC=C23)C=CC=N1

Pharmacology

Indication

Investigated for use/treatment in insomnia and sleep disorders.

Pharmacodynamics
Not Available
Mechanism of action
TargetActionsOrganism
UHistamine H1 receptor
inverse agonist
Human
U5-hydroxytryptamine receptor 2
inverse agonist
Human
UAlpha-2 adrenergic receptors
antagonist
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life

10 hours

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of adverse effects can be increased when Esmirtazapine is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of adverse effects can be increased when Esmirtazapine is combined with (S)-Warfarin.
2,5-Dimethoxy-4-ethylamphetamine2,5-Dimethoxy-4-ethylamphetamine may decrease the sedative and stimulatory activities of Esmirtazapine.
2,5-Dimethoxy-4-ethylthioamphetamine2,5-Dimethoxy-4-ethylthioamphetamine may decrease the sedative and stimulatory activities of Esmirtazapine.
3,4-Methylenedioxyamphetamine3,4-Methylenedioxyamphetamine may decrease the sedative and stimulatory activities of Esmirtazapine.
4-Bromo-2,5-dimethoxyamphetamine4-Bromo-2,5-dimethoxyamphetamine may decrease the sedative and stimulatory activities of Esmirtazapine.
4-hydroxycoumarinThe risk or severity of adverse effects can be increased when Esmirtazapine is combined with 4-hydroxycoumarin.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Methoxyamphetamine is combined with Esmirtazapine.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of adverse effects can be increased when Esmirtazapine is combined with 5-methoxy-N,N-dimethyltryptamine.
7-NitroindazoleThe risk or severity of adverse effects can be increased when 7-Nitroindazole is combined with Esmirtazapine.
Food Interactions
Not Available

References

General References
  1. Teegarden BR, Al Shamma H, Xiong Y: 5-HT(2A) inverse-agonists for the treatment of insomnia. Curr Top Med Chem. 2008;8(11):969-76. [PubMed:18673166]
  2. Lewis V: Undertreatment of menopausal symptoms and novel options for comprehensive management. Curr Med Res Opin. 2009 Nov;25(11):2689-98. doi: 10.1185/03007990903240519. [PubMed:19775194]
External Links
PubChem Compound
3085218
PubChem Substance
310264876
ChemSpider
2342166
ChEMBL
CHEMBL1366933
Wikipedia
Esmirtazapine

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentDyssomnias / Psychiatric Disorder NOS / Sleep disorders and disturbances / Sleep Disorders, Intrinsic / Sleep Initiation and Maintenance Disorder; Elderly1
3CompletedTreatmentDyssomnias / Psychiatric Disorder NOS / Sleep disorders and disturbances / Sleep Disorders, Intrinsic / Sleep Initiation and Maintenance Disorders1
3CompletedTreatmentDyssomnias / Psychiatric Disorder NOS / Sleep disorders and disturbances / Sleep Initiation and Maintenance Disorders / Sleeplessness1
3CompletedTreatmentMenopause / Postmenopausal Syndrome / Vasomotor Symptoms1
3CompletedTreatmentMenopause / Vasomotor Symptoms1
3CompletedTreatmentSleeplessness3
3TerminatedTreatmentDyssomnias / Psychiatric Disorder NOS / Sleep disorders and disturbances / Sleep Disorders, Intrinsic / Sleep Initiation and Maintenance Disorders1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)114 to 116Not Available
water solubilitySoluble in methanol and chloroform mg/mL (20 °C)Not Available
Predicted Properties
PropertyValueSource
Water Solubility1.1 mg/mLALOGPS
logP2.9ALOGPS
logP3.21ChemAxon
logS-2.4ALOGPS
pKa (Strongest Basic)6.67ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area19.37 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity82.66 m3·mol-1ChemAxon
Polarizability30.4 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as piperazinoazepines. These are compounds containing a piperazinoazepine skeleton, which consists of an azepine ring fused to a piperazine.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Piperazinoazepines
Sub Class
Not Available
Direct Parent
Piperazinoazepines
Alternative Parents
Benzazepines / Dialkylarylamines / N-methylpiperazines / Azepines / Aralkylamines / Pyridines and derivatives / Imidolactams / Benzenoids / Heteroaromatic compounds / Trialkylamines
show 3 more
Substituents
Benzazepine / Piperazino-azepine / Dialkylarylamine / Azepine / N-methylpiperazine / N-alkylpiperazine / Aralkylamine / Imidolactam / Benzenoid / Pyridine
show 12 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inverse agonist
General Function
Histamine receptor activity
Specific Function
In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamin...
Gene Name
HRH1
Uniprot ID
P35367
Uniprot Name
Histamine H1 receptor
Molecular Weight
55783.61 Da
References
  1. Ivgy-May N, Ruwe F, Krystal A, Roth T: Esmirtazapine in non-elderly adult patients with primary insomnia: efficacy and safety from a randomized, 6-week sleep laboratory trial. Sleep Med. 2015 Jul;16(7):838-44. doi: 10.1016/j.sleep.2015.04.001. Epub 2015 Apr 16. [PubMed:26047892]
Kind
Protein group
Organism
Human
Pharmacological action
Unknown
Actions
Inverse agonist
General Function
Virus receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodop...

Components:
References
  1. Ivgy-May N, Ruwe F, Krystal A, Roth T: Esmirtazapine in non-elderly adult patients with primary insomnia: efficacy and safety from a randomized, 6-week sleep laboratory trial. Sleep Med. 2015 Jul;16(7):838-44. doi: 10.1016/j.sleep.2015.04.001. Epub 2015 Apr 16. [PubMed:26047892]
Kind
Protein group
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Thioesterase binding
Specific Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazo...

Components:
References
  1. Ivgy-May N, Ruwe F, Krystal A, Roth T: Esmirtazapine in non-elderly adult patients with primary insomnia: efficacy and safety from a randomized, 6-week sleep laboratory trial. Sleep Med. 2015 Jul;16(7):838-44. doi: 10.1016/j.sleep.2015.04.001. Epub 2015 Apr 16. [PubMed:26047892]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Ramaekers JG, Conen S, de Kam PJ, Braat S, Peeters P, Theunissen EL, Ivgy-May N: Residual effects of esmirtazapine on actual driving performance: overall findings and an exploratory analysis into the role of CYP2D6 phenotype. Psychopharmacology (Berl). 2011 May;215(2):321-32. doi: 10.1007/s00213-010-2149-4. Epub 2011 Jan 19. [PubMed:21246188]
  2. Link [Link]

Drug created on March 19, 2008 10:48 / Updated on November 02, 2018 09:09