MIRTAZAPINE HYDROBROMIDE

Details

Stereochemistry	RACEMIC
Molecular Formula	C17H19N3.BrH
Molecular Weight	346.265
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Br.CN1CCN2C(C1)C3=CC=CC=C3CC4=CC=CN=C24

InChI

InChIKey=JERFRCPECXNTRC-UHFFFAOYSA-N

InChI=1S/C17H19N3.BrH/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;1H

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/11607047
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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Adrenergic receptor alpha-2 114 Target ID: CHEMBL2095158 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11607047	Antagonist 2849	7.0 null [pKi]
Serotonin 3 (5-HT3) receptor 59 Target ID: CHEMBL2094132 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11607047	Antagonist 2849	8.62 null [pKi]
Serotonin 2a (5-HT2a) receptor 237 Target ID: CHEMBL224 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11607047	Antagonist 2849	8.1 null [pKi]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Major depressive disorder 179 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020415s023s024.pdf	Primary		Approved 8583	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 1996

C_max

Value	Dose	Co-administered	Analyte	Population
32.3 μg/L REVIEW https://www.ncbi.nlm.nih.gov/pubmed/10885584	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

Value	Dose	Co-administered	Analyte	Population
345 μg × h/L REVIEW https://www.ncbi.nlm.nih.gov/pubmed/10885584	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
30 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020415s023s024.pdf	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
21.2 h REVIEW https://www.ncbi.nlm.nih.gov/pubmed/10885584	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

F_unbound

Value	Dose	Co-administered	Analyte	Population
15% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020415s023s024.pdf	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
15% REVIEW https://www.ncbi.nlm.nih.gov/pubmed/10885584	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

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946 inhibitor 2252	substrate 1193	substrate 1388 inhibitor 2507

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1741 CYP1A2 2153	CYP1A2 1197 BCRP 697

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP1A2 2333	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/31587356/	weak
CYP3A4 2633	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/31587356/	weak
CYP2D6 2546	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/31587356/	weak	no (co-administration study) Comment: mirtazapine caused no changes on the pharmacokinetics of paroxetine or amitriptyline Sources: https://pubmed.ncbi.nlm.nih.gov/31587356/
GLUT2 8	supressor 160 Sources: https://pubmed.ncbi.nlm.nih.gov/31231496/	yes
P-gp 1932	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/31587356/	yes

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP3A4 1946	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020415s034s036,021208s024s026lbl.pdf Page: 18.0	major	yes (co-administration study) Comment: ketoconazole increased mirtazapine AUC 50% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020415s034s036,021208s024s026lbl.pdf Page: 18.0
CYP2C9 1193	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/96/020415Orig1s000rev.pdf Page: 540.0	minor
BCRP 697	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/31037729/	yes
CYP1A2 1197	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020415s034s036,021208s024s026lbl.pdf Page: 17.0	yes	yes (co-administration study) Comment: cimetidine increaes mirtazapine AUC >50% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020415s034s036,021208s024s026lbl.pdf Page: 17.0
CYP2D6 1388	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020415s034s036,021208s024s026lbl.pdf Page: 17, 18	yes	yes (co-administration study) Comment: amitriptyline caused no changes on the pharmacokinetics of mirtazapine Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020415s034s036,021208s024s026lbl.pdf Page: 17, 18

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:6950	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:6950
ChemicalBook	CB0463388	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB0463388
ChemicalBook	CB7463387	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB7463387
eMolecules	591516	https://www.emolecules.com/cgi-bin/more?vid=591516
MolPort	MolPort-003-849-233	https://www.molport.com/shop/molecule-link/MolPort-003-849-233
Selleck Chemicals	mirtazapine-remeron-avanza	http://www.selleckchem.com/products/mirtazapine-remeron-avanza.html

PubMed

Title	Date	PubMed
Determination of mirtazapine and its demethyl metabolite in plasma by high-performance liquid chromatography with ultraviolet detection. Application to management of acute intoxication.	2002-08-05	12113982
Effects of antidepressants in rats trained to discriminate centrally administered isoproterenol.	2002-08	12130722
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.	2002-07-18	12109911
Body weight changes associated with psychopharmacology.	2002-07	12096167
Mirtazapine in the treatment of panic disorder.	2002-07	12090820
Separation of new antidepressants and their metabolites by micellar electrokinetic capillary chromatography.	2002-06-15	12015266
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.	2002-06	12095071
[Tolerability and efficacy of combined antidepressant therapy].	2002-05-25	12028939
Acute and chronic hypertensive headache and hypertensive encephalopathy.	2002-05	12100095
Urinary incontinence with mirtazapine.	2002-05	12019674
Dystonia induced by mirtazapine.	2002-05	12019672
An open-label, crossover trial of mirtazapine (15 and 30 mg) in cancer patients with pain and other distressing symptoms.	2002-05	12007762
Psychotropic drugs and the ECG: focus on the QTc interval.	2002-05	11996627
Spectrophotometric, spectrofluorimetric, HPLC and CZE determination of mirtazapine in pharmaceutical tablets.	2002-04-15	11929680
Venlafaxine and mirtazapine: different mechanisms of antidepressant action, common opioid-mediated antinociceptive effects--a possible opioid involvement in severe depression?	2002-04-05	11931344
Prevalence of sexual dysfunction among newer antidepressants.	2002-04	12000211
Mirtazapine overdose with benign outcome.	2002-04	11973120
Mirtazapine may have the propensity for developing a restless legs syndrome? A case report.	2002-04	11952928
Serotonin syndrome and atypical antipsychotics.	2002-04	11925312
Severe serotonin syndrome induced by mirtazapine monotherapy.	2002-04	11918514
Induction of hyperlocomotion in mice exposed to a novel environment by inhibition of serotonin reuptake. A pharmacological characterization of diverse classes of antidepressant agents.	2002-04	11888558
In the rat forced swimming test, NA-system mediated interactions may prevent the 5-HT properties of some subacute antidepressant treatments being expressed.	2002-04	11872334
Mirtazapine, yohimbine or olanzapine augmentation therapy for serotonin reuptake-associated female sexual dysfunction: a randomized, placebo controlled trial.	2002-03-12	11886692
Molecular characterisation of antidepressant effects in the mouse brain using gene expression profiling.	2002-03-12	11886689
Mirtazapine-induced akathisia.	2002-03-04	11999246
Sequential catecholamine and serotonin depletion in mirtazapine-treated depressed patients.	2002-03	12057033
New antidepressants in the treatment of neuropathic pain. A review.	2002-03	11981519
Successful treatment of recurrent brief depression with reboxetine -- a single case analysis.	2002-03	11951149
Effect of repeated treatment with mirtazapine on the central alpha1-adrenergic receptors.	2002-03	11939713
Heart rate variability as predictor of nonresponse to mirtazapine in panic disorder: a preliminary study.	2002-03	11892720
Intravenous mirtazapine in the treatment of depressed inpatients.	2002-02	11788241
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.	2002-01-31	11850045
A double-blind, placebo-controlled study of antidepressant augmentation with mirtazapine.	2002-01-15	11822997
A survey of prescribing practices in the treatment of depression.	2002-01	11853110
Chronic treatment with imipramine or mirtazapine antagonizes stress- and FG7142-induced increase in cortical norepinephrine output in freely moving rats.	2002-01	11746735
Permutation-validated principal components analysis of microarray data.	2002	11983060
Mania associated with mirtazapine augmentation of fluoxetine.	2002	11816053
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.	2001-12	11806859
Comment: serotonin syndrome induced by fluvoxamine and mirtazapine.	2001-12	11793645
An open trial of mirtazapine in menopausal women with depression unresponsive to estrogen replacement therapy.	2001-12	11788110
First report of mirtazapine-induced arthralgia.	2001-12	11777743
Relative safety of mirtazapine overdose.	2001-12	11757992
[Interference in the serotoninergic and noradrenergic system. Faster out of depression].	2001-11-01	11732403
Peripheral edema associated with mirtazapine.	2001-11	11724109
The effect of mirtazapine in panic disorder: an open label pilot study with a single-blind placebo run-in period.	2001-11	11712626
Trait anxiety and the effect of a single high dose of diazepam in unipolar depression.	2001-10-31	11684140
Efficacy of mirtazapine for prevention of depressive relapse: a placebo-controlled double-blind trial of recently remitted high-risk patients.	2001-10	11816867
[Pharmacotherapeutical approaches to insomnia patients with cardiac diseases and after heart transplantation].	2001-10	11757467
Third-generation antidepressants: do they offer advantages over the SSRIs?	2001	11735614
Meta-analytical studies on new antidepressants.	2001	11719915

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

0.1 uM mirtazapine affects glucocorticoid receptors expression (U937 cells)

Name

Type

Language

PYRAZINO(2,1-A)PYRIDO(2,3-C)(2)BENZAZEPINE, 1,2,3,4,4A,9-HEXAHYDRO-3-METHYL-, MONOHYDROBROMIDE

Preferred Name

English

MIRTAZAPINE HYDROBROMIDE

Common Name

English

PYRAZINO(2,1-A)PYRIDO(2,3-C)(2)BENZAZEPINE, 1,2,3,4,10,14B-HEXAHYDRO-2-METHYL-, HYDROBROMIDE (1:1)

Systematic Name

English

Code System Code Type Description

CAS

868363-97-7

Created by admin on Mon Mar 31 22:12:06 GMT 2025 , Edited by admin on Mon Mar 31 22:12:06 GMT 2025

PRIMARY

FDA UNII

R24NHR59AG

Created by admin on Mon Mar 31 22:12:06 GMT 2025 , Edited by admin on Mon Mar 31 22:12:06 GMT 2025

PRIMARY

PUBCHEM

11609903

Created by admin on Mon Mar 31 22:12:06 GMT 2025 , Edited by admin on Mon Mar 31 22:12:06 GMT 2025

PRIMARY

ACTIVE MOIETY


					A051Q2099Q

MIRTAZAPINE

SUBSTANCE RECORD


					R24NHR59AG

MIRTAZAPINE HYDROBROMIDE

Details

SMILES

InChI

CNS Activity

Originator

Approval Year

Targets

Conditions

Approved Use

Launch Date

Cmax

AUC

T1/2

Funbound

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Sourcing

PubMed

Patents

Sample Use Guides

C_max

T_1/2

F_unbound

Drug as perpetrator