U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry RACEMIC
Molecular Formula C17H19N3
Molecular Weight 265.3535
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of MIRTAZAPINE

SMILES

CN1CCN2C(C1)c3ccccc3Cc4cccnc42

InChI

InChIKey=RONZAEMNMFQXRA-UHFFFAOYSA-N
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

HIDE SMILES / InChI

Molecular Formula C17H19N3
Molecular Weight 265.3535
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

Description
Curator's Comment:: Description was created based on several sources, including: http://psychiatryonline.org/doi/10.1176/appi.books.9781585623860.as21#u2014-09-19T084532.264-0400d1e2463 http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020415s023s024.pdf

Mirtazapine, originally known as ORG 3770, was first synthesized by the Department of Medicinal Chemistry of NV Organon in the Netherlands (Kaspersen et al. 1989). First approved for use in major depression in the Netherlands in 1994, mirtazapine was introduced in the United States in 1996. The antidepressant mirtazapine has a dual mode of action. It is a noradrenergic and specific serotonergic antidepressant (NaSSA) that acts by antagonizing the adrenergic alpha2-autoreceptors and alpha2-heteroreceptors as well as by blocking 5-HT2 and 5-HT3 receptors. It enhances, therefore, the release of norepinephrine and 5-HT1A-mediated serotonergic transmission. This dual mode of action may conceivably be responsible for mirtazapine's rapid onset of action.

CNS Activity

Curator's Comment:: Mirtazapine entered the brain readily https://www.ncbi.nlm.nih.gov/pubmed/14726991

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
7.0 null [pKi]
8.62 null [pKi]
8.1 null [pKi]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
REMERON

Approved Use

REMERON (mirtazapine) Tablets are indicated for the treatment of major depressive disorder. The efficacy of REMERON in the treatment of major depressive disorder was established in 6-week controlled trials of outpatients whose diagnoses corresponded most closely to the Diagnostic and Statistical Manual of Mental Disorders – 3rd edition (DSM-III) category of major depressive disorder (see CLINICAL PHARMACOLOGY). A major depressive episode (DSM-IV) implies a prominent and relatively persistent (nearly every day for at least 2 weeks) depressed or dysphoric mood that usually interferes with daily functioning, and includes at least 5 of the following 9 symptoms: depressed mood, loss of interest in usual activities, significant change in weight and/or appetite, insomnia or hypersomnia, psychomotor agitation or retardation, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, a suicide attempt, or suicidal ideation. The effectiveness of REMERON in hospitalized depressed patients has not been adequately studied. The efficacy of REMERON in maintaining a response in patients with major depressive disorder for up to 40 weeks following 8 to 12 weeks of initial open-label treatment was demonstrated in a placebo-controlled trial. Nevertheless, the physician who elects to use REMERON for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient (see CLINICAL PHARMACOLOGY).

Launch Date

8.3471041E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
32.3 μg/L
15 mg single, oral
dose: 15 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MIRTAZAPINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
345 μg × h/L
15 mg single, oral
dose: 15 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MIRTAZAPINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
21.2 h
15 mg single, oral
dose: 15 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MIRTAZAPINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
30 h
15 mg single, oral
dose: 15 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MIRTAZAPINE plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
15%
15 mg single, oral
dose: 15 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MIRTAZAPINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
15%
15 mg single, oral
dose: 15 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MIRTAZAPINE plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
75 mg single, oral
Highest studied dose
Dose: 75 mg
Route: oral
Route: single
Dose: 75 mg
Sources:
healthy, 18-35 years
Health Status: healthy
Age Group: 18-35 years
Sex: M
Sources:
15 mg 1 times / day steady, oral
Recommended
Dose: 15 mg, 1 times / day
Route: oral
Route: steady
Dose: 15 mg, 1 times / day
Sources:
unhealthy, 55 years
n = 1
Health Status: unhealthy
Age Group: 55 years
Sex: F
Population Size: 1
Sources:
Disc. AE: Angle closure glaucoma...
AEs leading to
discontinuation/dose reduction:
Angle closure glaucoma (1 patient)
Sources:
15 mg 1 times / day steady, oral
Recommended
Dose: 15 mg, 1 times / day
Route: oral
Route: steady
Dose: 15 mg, 1 times / day
Sources:
unhealthy, adult
n = 453
Health Status: unhealthy
Age Group: adult
Population Size: 453
Sources:
Disc. AE: Somnolence, Nausea...
AEs leading to
discontinuation/dose reduction:
Somnolence (10.4%)
Nausea (1.5%)
Sources:
15 mg 1 times / day multiple, oral
Recommended
Dose: 15 mg, 1 times / day
Route: oral
Route: multiple
Dose: 15 mg, 1 times / day
Sources:
unhealthy, children
Health Status: unhealthy
Condition: major depressive disorde
Age Group: children
Sex: M+F
Sources:
Other AEs: Suicidal tendency, Suicidal behavior...
AEs

AEs

AESignificanceDosePopulation
Angle closure glaucoma 1 patient
Disc. AE
15 mg 1 times / day steady, oral
Recommended
Dose: 15 mg, 1 times / day
Route: oral
Route: steady
Dose: 15 mg, 1 times / day
Sources:
unhealthy, 55 years
n = 1
Health Status: unhealthy
Age Group: 55 years
Sex: F
Population Size: 1
Sources:
Nausea 1.5%
Disc. AE
15 mg 1 times / day steady, oral
Recommended
Dose: 15 mg, 1 times / day
Route: oral
Route: steady
Dose: 15 mg, 1 times / day
Sources:
unhealthy, adult
n = 453
Health Status: unhealthy
Age Group: adult
Population Size: 453
Sources:
Somnolence 10.4%
Disc. AE
15 mg 1 times / day steady, oral
Recommended
Dose: 15 mg, 1 times / day
Route: oral
Route: steady
Dose: 15 mg, 1 times / day
Sources:
unhealthy, adult
n = 453
Health Status: unhealthy
Age Group: adult
Population Size: 453
Sources:
Suicidal behavior
15 mg 1 times / day multiple, oral
Recommended
Dose: 15 mg, 1 times / day
Route: oral
Route: multiple
Dose: 15 mg, 1 times / day
Sources:
unhealthy, children
Health Status: unhealthy
Condition: major depressive disorde
Age Group: children
Sex: M+F
Sources:
Suicidal tendency
15 mg 1 times / day multiple, oral
Recommended
Dose: 15 mg, 1 times / day
Route: oral
Route: multiple
Dose: 15 mg, 1 times / day
Sources:
unhealthy, children
Health Status: unhealthy
Condition: major depressive disorde
Age Group: children
Sex: M+F
Sources:
Overview

OverviewOther

Other InhibitorOther SubstrateOther Inducer




Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
weak
weak
weak
no (co-administration study)
Comment: mirtazapine caused no changes on the pharmacokinetics of paroxetine or amitriptyline
yes
yes
Drug as victim

Drug as victim

PubMed

PubMed

TitleDatePubMed
Third-generation antidepressants: do they offer advantages over the SSRIs?
2001
Meta-analytical studies on new antidepressants.
2001
Do some antidepressants work faster than others?
2001
Pharmacology of rapid-onset antidepressant treatment strategies.
2001
Long-term treatment with antidepressant drugs reduces the sensitivity of cortical cholinergic neurons to the activating actions of stress and the anxiogenic drug FG 7142.
2001 Aug
Mirtazapine versus venlafaxine in hospitalized severely depressed patients with melancholic features.
2001 Aug
Meta-analysis of placebo-controlled trials with mirtazapine using the core items of the Hamilton Depression Scale as evidence of a pure antidepressive effect in the short-term treatment of major depression.
2001 Dec
Comment: serotonin syndrome induced by fluvoxamine and mirtazapine.
2001 Dec
First report of mirtazapine-induced arthralgia.
2001 Dec
Relative safety of mirtazapine overdose.
2001 Dec
Serotonin syndrome: early management with cyproheptadine.
2001 Jul-Aug
A placebo-controlled, crossover trial of granisetron in SRI-induced sexual dysfunction.
2001 Jun
Peripheral edema associated with mirtazapine.
2001 Nov
[Interference in the serotoninergic and noradrenergic system. Faster out of depression].
2001 Nov 1
Efficacy of mirtazapine for prevention of depressive relapse: a placebo-controlled double-blind trial of recently remitted high-risk patients.
2001 Oct
[Pharmacotherapeutical approaches to insomnia patients with cardiac diseases and after heart transplantation].
2001 Oct
Mirtazapine may be useful in treating nausea and insomnia of cancer chemotherapy.
2001 Sep
Permutation-validated principal components analysis of microarray data.
2002
Mania associated with mirtazapine augmentation of fluoxetine.
2002
Mirtazapine overdose with benign outcome.
2002 Apr
Mirtazapine may have the propensity for developing a restless legs syndrome? A case report.
2002 Apr
Serotonin syndrome and atypical antipsychotics.
2002 Apr
Severe serotonin syndrome induced by mirtazapine monotherapy.
2002 Apr
Induction of hyperlocomotion in mice exposed to a novel environment by inhibition of serotonin reuptake. A pharmacological characterization of diverse classes of antidepressant agents.
2002 Apr
In the rat forced swimming test, NA-system mediated interactions may prevent the 5-HT properties of some subacute antidepressant treatments being expressed.
2002 Apr
Spectrophotometric, spectrofluorimetric, HPLC and CZE determination of mirtazapine in pharmaceutical tablets.
2002 Apr 15
Effects of antidepressants in rats trained to discriminate centrally administered isoproterenol.
2002 Aug
Determination of mirtazapine and its demethyl metabolite in plasma by high-performance liquid chromatography with ultraviolet detection. Application to management of acute intoxication.
2002 Aug 5
Intravenous mirtazapine in the treatment of depressed inpatients.
2002 Feb
Venlafaxine and mirtazapine: different mechanisms of antidepressant action, common opioid-mediated antinociceptive effects--a possible opioid involvement in severe depression?
2002 Feb-Apr
A survey of prescribing practices in the treatment of depression.
2002 Jan
Chronic treatment with imipramine or mirtazapine antagonizes stress- and FG7142-induced increase in cortical norepinephrine output in freely moving rats.
2002 Jan
A double-blind, placebo-controlled study of antidepressant augmentation with mirtazapine.
2002 Jan 15
Mirtazapine, but not fluvoxamine, normalizes the blunted REM sleep response to clonidine in depressed patients: implications for subsensitivity of alpha(2)-adrenergic receptors in depression.
2002 Jan 31
Body weight changes associated with psychopharmacology.
2002 Jul
Mirtazapine in the treatment of panic disorder.
2002 Jul
Synthesis and pharmacological testing of 1,2,3,4,10,14b-hexahydro-6-methoxy-2-methyldibenzo[c,f]pyrazino[1,2-a]azepin and its enantiomers in comparison with the two antidepressants mianserin and mirtazapine.
2002 Jul 18
Prevention of the stress-induced increase in the concentration of neuroactive steroids in rat brain by long-term administration of mirtazapine but not of fluoxetine.
2002 Jun
Sequential catecholamine and serotonin depletion in mirtazapine-treated depressed patients.
2002 Mar
New antidepressants in the treatment of neuropathic pain. A review.
2002 Mar
Successful treatment of recurrent brief depression with reboxetine -- a single case analysis.
2002 Mar
Effect of repeated treatment with mirtazapine on the central alpha1-adrenergic receptors.
2002 Mar
Heart rate variability as predictor of nonresponse to mirtazapine in panic disorder: a preliminary study.
2002 Mar
Mirtazapine-induced akathisia.
2002 Mar 4
[Tolerability and efficacy of combined antidepressant therapy].
2002 Mar-Apr
Acute and chronic hypertensive headache and hypertensive encephalopathy.
2002 May
Urinary incontinence with mirtazapine.
2002 May
Psychotropic drugs and the ECG: focus on the QTc interval.
2002 May
Mirtazapine, yohimbine or olanzapine augmentation therapy for serotonin reuptake-associated female sexual dysfunction: a randomized, placebo controlled trial.
2002 May-Jun
Molecular characterisation of antidepressant effects in the mouse brain using gene expression profiling.
2002 May-Jun
Patents

Sample Use Guides

The recommended starting dose for REMERON® (mirtazapine) Tablets is 15 mg/day, administered in a single dose. In the controlled clinical trials establishing the efficacy of REMERON in the treatment of major depressive disorder, the effective dose range was generally 15 to 45 mg/day.
Route of Administration: Oral
0.1 uM mirtazapine affects glucocorticoid receptors expression (U937 cells)
Substance Class Chemical
Created
by admin
on Fri Jun 25 20:57:41 UTC 2021
Edited
by admin
on Fri Jun 25 20:57:41 UTC 2021
Record UNII
A051Q2099Q
Record Status Validated (UNII)
Record Version
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Name Type Language
MIRTAZAPINE
EP   INN   JAN   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD  
INN   USAN  
Official Name English
ORG-3770
Code English
MIRTAZAPINE [USAN]
Common Name English
MIRTAZAPINE ANHYDROUS
Common Name English
REMERON
Brand Name English
MIRTAZAPINE, (+/-)-
Common Name English
MIRTAZAPINE [ORANGE BOOK]
Common Name English
MIRTAZAPINE [USP MONOGRAPH]
Common Name English
ZISPIN
Brand Name English
1,2,3,4,10,14B-HEXAHYDRO-2-METHYLPYRAZINO(2,1-A)PYRIDO(2,3-C)BENZAZEPINE
Common Name English
MIRATAZ
Brand Name English
MIRTAZAPINE [WHO-DD]
Common Name English
PYRAZINO(2,1-A)PYRIDO(2,3-C)(2)BENZAZEPINE, 1,2,3,4,10,14B-HEXAHYDRO-2-METHYL-
Common Name English
NORSET
Brand Name English
MIRTAZAPINE [JAN]
Common Name English
MIRTAZAPINE [GREEN BOOK]
Common Name English
MIRTAZAPINE [USP-RS]
Common Name English
MIRTAZAPINE [MI]
Common Name English
REXER
Brand Name English
AVANZA
Brand Name English
MIRTAZAPIN
Common Name English
ORG 3770
Code English
MIRTAZAPINE [INN]
Common Name English
6-AZAMIANSERIN
Common Name English
MIRTAZAPINE [VANDF]
Common Name English
MIRTAZAPINE [EP MONOGRAPH]
Common Name English
PROMYRTIL
Brand Name English
Classification Tree Code System Code
LIVERTOX 643
Created by admin on Fri Jun 25 20:57:41 UTC 2021 , Edited by admin on Fri Jun 25 20:57:41 UTC 2021
WHO-ATC N06AX11
Created by admin on Fri Jun 25 20:57:41 UTC 2021 , Edited by admin on Fri Jun 25 20:57:41 UTC 2021
NCI_THESAURUS C265
Created by admin on Fri Jun 25 20:57:41 UTC 2021 , Edited by admin on Fri Jun 25 20:57:41 UTC 2021
WHO-VATC QN06AX11
Created by admin on Fri Jun 25 20:57:41 UTC 2021 , Edited by admin on Fri Jun 25 20:57:41 UTC 2021
Code System Code Type Description
USP_CATALOG
1444279
Created by admin on Fri Jun 25 20:57:41 UTC 2021 , Edited by admin on Fri Jun 25 20:57:41 UTC 2021
PRIMARY USP-RS
CAS
85650-52-8
Created by admin on Fri Jun 25 20:57:41 UTC 2021 , Edited by admin on Fri Jun 25 20:57:41 UTC 2021
PRIMARY
IUPHAR
7241
Created by admin on Fri Jun 25 20:57:41 UTC 2021 , Edited by admin on Fri Jun 25 20:57:41 UTC 2021
PRIMARY
DRUG BANK
DB00370
Created by admin on Fri Jun 25 20:57:41 UTC 2021 , Edited by admin on Fri Jun 25 20:57:41 UTC 2021
PRIMARY
INN
6481
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PRIMARY
RXCUI
15996
Created by admin on Fri Jun 25 20:57:41 UTC 2021 , Edited by admin on Fri Jun 25 20:57:41 UTC 2021
PRIMARY RxNorm
ECHA (EC/EINECS)
288-060-6
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PRIMARY
PUBCHEM
4205
Created by admin on Fri Jun 25 20:57:41 UTC 2021 , Edited by admin on Fri Jun 25 20:57:41 UTC 2021
PRIMARY
LACTMED
Mirtazapine
Created by admin on Fri Jun 25 20:57:41 UTC 2021 , Edited by admin on Fri Jun 25 20:57:41 UTC 2021
PRIMARY
WIKIPEDIA
MIRTAZAPINE
Created by admin on Fri Jun 25 20:57:41 UTC 2021 , Edited by admin on Fri Jun 25 20:57:41 UTC 2021
PRIMARY
MERCK INDEX
M7561
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PRIMARY Merck Index
ChEMBL
CHEMBL654
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PRIMARY
EVMPD
SUB08996MIG
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PRIMARY
DRUG CENTRAL
1816
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PRIMARY
MESH
C035133
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PRIMARY
FDA UNII
A051Q2099Q
Created by admin on Fri Jun 25 20:57:41 UTC 2021 , Edited by admin on Fri Jun 25 20:57:41 UTC 2021
PRIMARY
NCI_THESAURUS
C29265
Created by admin on Fri Jun 25 20:57:41 UTC 2021 , Edited by admin on Fri Jun 25 20:57:41 UTC 2021
PRIMARY
CAS
61337-67-5
Created by admin on Fri Jun 25 20:57:41 UTC 2021 , Edited by admin on Fri Jun 25 20:57:41 UTC 2021
SUPERSEDED
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ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC
NOAEL TOXICITY