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

Details

Stereochemistry ACHIRAL
Molecular Formula C20H23N
Molecular Weight 277.4041
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of MAPROTILINE

SMILES

CNCCCC12CCC(c3ccccc31)c4ccccc42

InChI

InChIKey=QSLMDECMDJKHMQ-UHFFFAOYSA-N
InChI=1S/C20H23N/c1-21-14-6-12-20-13-11-15(16-7-2-4-9-18(16)20)17-8-3-5-10-19(17)20/h2-5,7-10,15,21H,6,11-14H2,1H3

HIDE SMILES / InChI

Molecular Formula C20H23N
Molecular Weight 277.4041
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Maprotiline is a tetracyclic antidepressant with similar pharmacological properties to tricyclic antidepressants (TCAs). Similar to TCAs, maprotiline inhibits neuronal norepinephrine reuptake, possesses some anticholinergic activity, and does not affect monoamine oxidase activity. It differs from TCAs in that it does not appear to block serotonin reuptake. Maprotiline may be used to treat depressive affective disorders, including dysthymic disorder (depressive neurosis) and major depressive disorder. Maprotiline is effective at reducing symptoms of anxiety associated with depression. The mechanism of action of maprotiline is not precisely known. It does not act primarily by stimulation of the central nervous system and is not a monoamine oxidase inhibitor. The postulated mechanism of maprotiline is that it acts primarily by potentiation of central adrenergic synapses by blocking reuptake of norepinephrine at nerve endings. This pharmacologic action is thought to be responsible for the drug’s antidepressant and anxiolytic effects. The mean time to peak is 12 hours. The half-life of elimination averages 51 hours.

Originator

Curator's Comment:: # Swiss manufacturer Geigy (now Novartis) since the early 1980's

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
MAPROTILINE HYDROCHLORIDE

Approved Use

Maprotiline hydrochloride tablets are indicated for the treatment of depressive illness in patients with depressive neurosis (dysthymic disorder) and manic depressive illness, depressed type (major depressive disorder). Maprotiline is also effective for the relief of anxiety associated with de pression.

Launch Date

5.9175358E11
Primary
MAPROTILINE HYDROCHLORIDE

Approved Use

Maprotiline hydrochloride tablets are indicated for the treatment of depressive illness in patients with depressive neurosis (dysthymic disorder) and manic depressive illness, depressed type (major depressive disorder). Maprotiline is also effective for the relief of anxiety associated with de pression.

Launch Date

5.9175358E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
139 ng/mL
125 mg single, oral
dose: 125 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MAPROTILINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE
food status: FASTED
17.6 ng/mL
75 mg single, oral
dose: 75 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MAPROTILINE plasma
Homo sapiens
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
3244 ng × h/mL
125 mg single, oral
dose: 125 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MAPROTILINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
44.3 h
75 mg single, oral
dose: 75 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MAPROTILINE plasma
Homo sapiens
Doses

Doses

DosePopulationAdverse events​
75 mg 1 times / day multiple, oral (starting)
Dose: 75 mg, 1 times / day
Route: oral
Route: multiple
Dose: 75 mg, 1 times / day
Sources:
unhealthy
Health Status: unhealthy
Condition: depressive illness
Sources:
Other AEs: Nervousness, Anxiety...
Other AEs:
Nervousness (6%)
Anxiety (3%)
Insomnia (2%)
Agitation (2%)
Drowsiness (16%)
Dizziness (8%)
Tremor (3%)
Dry mouth (22%)
Constipation (6%)
Blurred vision (4%)
Nausea (2%)
Weakness (4%)
Headache (4%)
Fatigue (4%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Drowsiness 16%
75 mg 1 times / day multiple, oral (starting)
Dose: 75 mg, 1 times / day
Route: oral
Route: multiple
Dose: 75 mg, 1 times / day
Sources:
unhealthy
Health Status: unhealthy
Condition: depressive illness
Sources:
Agitation 2%
75 mg 1 times / day multiple, oral (starting)
Dose: 75 mg, 1 times / day
Route: oral
Route: multiple
Dose: 75 mg, 1 times / day
Sources:
unhealthy
Health Status: unhealthy
Condition: depressive illness
Sources:
Insomnia 2%
75 mg 1 times / day multiple, oral (starting)
Dose: 75 mg, 1 times / day
Route: oral
Route: multiple
Dose: 75 mg, 1 times / day
Sources:
unhealthy
Health Status: unhealthy
Condition: depressive illness
Sources:
Nausea 2%
75 mg 1 times / day multiple, oral (starting)
Dose: 75 mg, 1 times / day
Route: oral
Route: multiple
Dose: 75 mg, 1 times / day
Sources:
unhealthy
Health Status: unhealthy
Condition: depressive illness
Sources:
Dry mouth 22%
75 mg 1 times / day multiple, oral (starting)
Dose: 75 mg, 1 times / day
Route: oral
Route: multiple
Dose: 75 mg, 1 times / day
Sources:
unhealthy
Health Status: unhealthy
Condition: depressive illness
Sources:
Anxiety 3%
75 mg 1 times / day multiple, oral (starting)
Dose: 75 mg, 1 times / day
Route: oral
Route: multiple
Dose: 75 mg, 1 times / day
Sources:
unhealthy
Health Status: unhealthy
Condition: depressive illness
Sources:
Tremor 3%
75 mg 1 times / day multiple, oral (starting)
Dose: 75 mg, 1 times / day
Route: oral
Route: multiple
Dose: 75 mg, 1 times / day
Sources:
unhealthy
Health Status: unhealthy
Condition: depressive illness
Sources:
Blurred vision 4%
75 mg 1 times / day multiple, oral (starting)
Dose: 75 mg, 1 times / day
Route: oral
Route: multiple
Dose: 75 mg, 1 times / day
Sources:
unhealthy
Health Status: unhealthy
Condition: depressive illness
Sources:
Fatigue 4%
75 mg 1 times / day multiple, oral (starting)
Dose: 75 mg, 1 times / day
Route: oral
Route: multiple
Dose: 75 mg, 1 times / day
Sources:
unhealthy
Health Status: unhealthy
Condition: depressive illness
Sources:
Headache 4%
75 mg 1 times / day multiple, oral (starting)
Dose: 75 mg, 1 times / day
Route: oral
Route: multiple
Dose: 75 mg, 1 times / day
Sources:
unhealthy
Health Status: unhealthy
Condition: depressive illness
Sources:
Weakness 4%
75 mg 1 times / day multiple, oral (starting)
Dose: 75 mg, 1 times / day
Route: oral
Route: multiple
Dose: 75 mg, 1 times / day
Sources:
unhealthy
Health Status: unhealthy
Condition: depressive illness
Sources:
Constipation 6%
75 mg 1 times / day multiple, oral (starting)
Dose: 75 mg, 1 times / day
Route: oral
Route: multiple
Dose: 75 mg, 1 times / day
Sources:
unhealthy
Health Status: unhealthy
Condition: depressive illness
Sources:
Nervousness 6%
75 mg 1 times / day multiple, oral (starting)
Dose: 75 mg, 1 times / day
Route: oral
Route: multiple
Dose: 75 mg, 1 times / day
Sources:
unhealthy
Health Status: unhealthy
Condition: depressive illness
Sources:
Dizziness 8%
75 mg 1 times / day multiple, oral (starting)
Dose: 75 mg, 1 times / day
Route: oral
Route: multiple
Dose: 75 mg, 1 times / day
Sources:
unhealthy
Health Status: unhealthy
Condition: depressive illness
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG



OverviewOther

Other InhibitorOther SubstrateOther Inducer

Drug as perpetrator​

Drug as perpetrator​

Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
likely
likely (co-administration study)
Comment: Relevant inhibition of the desmethylmaprotiline formation rate was observed in incubations with quinidine, furafylline and ketoconazole only
yes
likely (co-administration study)
Comment: Relevant inhibition of the desmethylmaprotiline formation rate was observed in incubations with quinidine, furafylline and ketoconazole only
yes
likely (co-administration study)
Comment: Relevant inhibition of the desmethylmaprotiline formation rate was observed in incubations with quinidine, furafylline and ketoconazole only
Tox targets

Tox targets

PubMed

PubMed

TitleDatePubMed
The serotonin syndrome.
1992 Oct
Effects of psychotropic drugs on seizure threshold.
2002
Simultaneous quantification of citalopram, clozapine, fluoxetine, norfluoxetine, maprotiline, desmethylmaprotiline and trazodone in human serum by HPLC analysis.
2002 Dec
The effects of tricyclic antidepressants on breast cancer risk.
2002 Jan 7
Clinical trials with hypericum extracts in patients with depression--results, comparisons, conclusions for therapy with antidepressant drugs.
2002 Jul
Neurochemical and behavioural characterization of milnacipran, a serotonin and noradrenaline reuptake inhibitor in rats.
2002 Jul
An investigation of monoamine receptors involved in antinociceptive effects of antidepressants.
2002 Jul
[Tolerability and efficacy of combined antidepressant therapy].
2002 Mar-Apr
[Depression and epilepsy].
2002 Sep 16-30
[Effects of escitalopram on anxiety symptoms in depression].
2002 Sep-Oct
[Current views on migraine and anti-migraine preparations].
2003
[11C]-DASB, a tool for in vivo measurement of SSRI-induced occupancy of the serotonin transporter: PET characterization and evaluation in cats.
2003 Feb
Chronic treatment with antidepressants decreases intraoperative core hypothermia.
2003 Jul
Bi-phasic change in BDNF gene expression following antidepressant drug treatment.
2003 Jun
Olanzapine in the treatment-resistant, combat-related PTSD--a series of case reports.
2003 May
Tricyclic antidepressants as long-acting local anesthetics.
2003 May
In vivo measurement of the serotonin transporter with (S)-([18F]fluoromethyl)-(+)-McN5652.
2003 Nov
Effects of some antidepressant drugs on tryptaminergic responses of the rat jejunum.
2003 Oct
A comparative solid-phase extraction study for the simultaneous determination of fluoxetine, amitriptyline, nortriptyline, trimipramine, maprotiline, clomipramine, and trazodone in whole blood by capillary gas-liquid chromatography with nitrogen-phosphorus detection.
2003 Sep
[Placebo to antidepressant effects ratio by electroencephalographic data].
2004
Effect of the antidepressant maprotiline on calcium movement and the viability of renal tubular cells.
2004 Aug
Human liver aldehyde oxidase: inhibition by 239 drugs.
2004 Jan
Effect of maprotiline on Ca(2+) movement in human neuroblastoma cells.
2004 Jul 16
[Comparative observation on efficacy of jieyu pill and maprotiline in treating depression].
2004 May
Serotonin and noradrenaline reuptake inhibitors in animal models of pain.
2004 Oct
Inhibition of G protein-activated inwardly rectifying K+ channels by various antidepressant drugs.
2004 Oct
Clinical study on electro-acupuncture treatment for 30 cases of mental depression.
2004 Sep
Tricyclic antidepressants, QT interval prolongation, and torsade de pointes.
2004 Sep-Oct
Frontotemporal arachnoid cyst connected to relapsing stupor.
2004 Winter
Contribution of sleep research to the development of new antidepressants.
2005
Dose-response relationship of recent antidepressants in the short-term treatment of depression.
2005
The AGNP-TDM Expert Group Consensus Guidelines: focus on therapeutic monitoring of antidepressants.
2005
Reduction of Submissive Behavior Model for antidepressant drug activity testing: study using a video-tracking system.
2005 Dec
[(11)C]MADAM, a new serotonin transporter radioligand characterized in the monkey brain by PET.
2005 Dec 1
Development of a solid phase extraction for 13 'new' generation antidepressants and their active metabolites for gas chromatographic-mass spectrometric analysis.
2005 Dec 9
Analgesic therapy in postherpetic neuralgia: a quantitative systematic review.
2005 Jul
Comparative evaluation of positron emission tomography radiotracers for imaging the norepinephrine transporter: (S,S) and (R,R) enantiomers of reboxetine analogs ([11C]methylreboxetine, 3-Cl-[11C]methylreboxetine and [18F]fluororeboxetine), (R)-[11C]nisoxetine, [11C]oxaprotiline and [11C]lortalamine.
2005 Jul
Internet-based search of randomised trials relevant to mental health originating in the Arab world.
2005 Jul 26
[Evaluation of antidepressant activity in a model of depressionlike state due to social isolation in rats].
2005 Jul-Aug
Effect of long-term administration of antidepressants on the lipid composition of brain plasma membranes.
2005 Jun
[Detection of maprotiline and proserine in forensic medical examination of cadaver].
2005 Mar-Apr
Citalopram associated with acute angle-closure glaucoma: case report.
2005 Oct 4
Changes in AMPA subunit expression in the mouse brain after chronic treatment with the antidepressant maprotiline: a link between noradrenergic and glutamatergic function?
2006 Apr
A fully automated turbulent-flow liquid chromatography-tandem mass spectrometry technique for monitoring antidepressants in human serum.
2006 Feb
Inhibition of cardiac HERG potassium channels by antidepressant maprotiline.
2006 Feb 15
Dopamine release in human neocortical slices: characterization of inhibitory autoreceptors and of nicotinic acetylcholine receptor-evoked release.
2006 Jan 30
Are the effects of the antidepressants amitriptyline, maprotiline, and fluoxetine on inhibitory avoidance state-dependent?
2006 Jan 6
Increasing synaptic noradrenaline, serotonin and histamine enhances in vivo binding of phosphodiesterase-4 inhibitor (R)-[11C]rolipram in rat brain, lung and heart.
2006 Jun 20
Age-dependent interactive changes in serotonergic and noradrenergic cortical axon terminals in F344 rats.
2006 Mar
Phosducin-like protein levels in leukocytes of patients with major depression and in rat cortex: the effect of chronic treatment with antidepressants.
2006 Mar 30
Patents

Patents

Sample Use Guides

Initial Adult Dosage: 75 mg daily is suggested for outpatients with mild to moderate depression. However, in some patients, particularly the elderly, an initial dosage of 25 mg daily may be used. Because of the long half-life of maprotiline, the initial dosage should be maintained for 2 weeks. The dosage may then be increased gradually in 25 mg increments as required and tolerated. In most outpatients a maximum dose of 150 mg daily More severely depressed, hospitalized patients should be given an initial daily dose of 100 mg to 150 mg which may be gradually increased as required and tolerated. Most hospitalized patients with moderate to severe depression respond to a daily dose of 150 mg although dosages as high as 225 mg may be re quired in some cases. Daily dosage of 225 mg should not be exceeded. Elderly Patients: In general, lower dosages are recommended for patients over 60 years of age. Dosages of 50 mg to 75 mg daily are usually satisfactory as maintenance therapy for elderly patients who do not tolerate higher amounts.
Route of Administration: Oral
Maprotiline inhibited hERG currents with an IC(50) of 8.2 micromol/l in HEK cells and 29.2 micromol/l in Xenopus oocytes
Substance Class Chemical
Created
by admin
on Sat Jun 26 04:42:42 UTC 2021
Edited
by admin
on Sat Jun 26 04:42:42 UTC 2021
Record UNII
2U1W68TROF
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
MAPROTILINE
INN   MART.   MI   USAN   VANDF   WHO-DD  
USAN   INN  
Official Name English
N-METHYL-9,10-ETHANOANTHRACENE-9(10H)-PROPYLAMINE
Systematic Name English
BA-34,276 FREE BASE
Code English
MAPROTILINE [MART.]
Common Name English
MAPROTILINE [WHO-DD]
Common Name English
MAPROTILINE [INN]
Common Name English
MAPROTILINE [MI]
Common Name English
MAPROTILINE [USAN]
Common Name English
BA-34276 FREE BASE
Code English
9,10-ETHANOANTHRACENE-9(10H)-PROPANAMINE, N-METHYL-
Systematic Name English
MAPROTILINE [VANDF]
Common Name English
Classification Tree Code System Code
LIVERTOX 581
Created by admin on Sat Jun 26 04:42:42 UTC 2021 , Edited by admin on Sat Jun 26 04:42:42 UTC 2021
WHO-ATC N06AA21
Created by admin on Sat Jun 26 04:42:42 UTC 2021 , Edited by admin on Sat Jun 26 04:42:42 UTC 2021
WHO-VATC QN06AA21
Created by admin on Sat Jun 26 04:42:42 UTC 2021 , Edited by admin on Sat Jun 26 04:42:42 UTC 2021
NCI_THESAURUS C265
Created by admin on Sat Jun 26 04:42:42 UTC 2021 , Edited by admin on Sat Jun 26 04:42:42 UTC 2021
Code System Code Type Description
EPA CompTox
10262-69-8
Created by admin on Sat Jun 26 04:42:42 UTC 2021 , Edited by admin on Sat Jun 26 04:42:42 UTC 2021
PRIMARY
NCI_THESAURUS
C61824
Created by admin on Sat Jun 26 04:42:42 UTC 2021 , Edited by admin on Sat Jun 26 04:42:42 UTC 2021
PRIMARY
DRUG CENTRAL
1634
Created by admin on Sat Jun 26 04:42:42 UTC 2021 , Edited by admin on Sat Jun 26 04:42:42 UTC 2021
PRIMARY
ECHA (EC/EINECS)
233-599-4
Created by admin on Sat Jun 26 04:42:42 UTC 2021 , Edited by admin on Sat Jun 26 04:42:42 UTC 2021
PRIMARY
DRUG BANK
DB00934
Created by admin on Sat Jun 26 04:42:42 UTC 2021 , Edited by admin on Sat Jun 26 04:42:42 UTC 2021
PRIMARY
LACTMED
Maprotiline
Created by admin on Sat Jun 26 04:42:42 UTC 2021 , Edited by admin on Sat Jun 26 04:42:42 UTC 2021
PRIMARY
MERCK INDEX
M7083
Created by admin on Sat Jun 26 04:42:42 UTC 2021 , Edited by admin on Sat Jun 26 04:42:42 UTC 2021
PRIMARY Merck Index
CAS
10262-69-8
Created by admin on Sat Jun 26 04:42:42 UTC 2021 , Edited by admin on Sat Jun 26 04:42:42 UTC 2021
PRIMARY
ChEMBL
CHEMBL21731
Created by admin on Sat Jun 26 04:42:42 UTC 2021 , Edited by admin on Sat Jun 26 04:42:42 UTC 2021
PRIMARY
INN
2763
Created by admin on Sat Jun 26 04:42:42 UTC 2021 , Edited by admin on Sat Jun 26 04:42:42 UTC 2021
PRIMARY
EVMPD
SUB08647MIG
Created by admin on Sat Jun 26 04:42:42 UTC 2021 , Edited by admin on Sat Jun 26 04:42:42 UTC 2021
PRIMARY
FDA UNII
2U1W68TROF
Created by admin on Sat Jun 26 04:42:42 UTC 2021 , Edited by admin on Sat Jun 26 04:42:42 UTC 2021
PRIMARY
WIKIPEDIA
MAPROTILINE
Created by admin on Sat Jun 26 04:42:42 UTC 2021 , Edited by admin on Sat Jun 26 04:42:42 UTC 2021
PRIMARY
PUBCHEM
4011
Created by admin on Sat Jun 26 04:42:42 UTC 2021 , Edited by admin on Sat Jun 26 04:42:42 UTC 2021
PRIMARY
RXCUI
6646
Created by admin on Sat Jun 26 04:42:42 UTC 2021 , Edited by admin on Sat Jun 26 04:42:42 UTC 2021
PRIMARY RxNorm
IUPHAR
2402
Created by admin on Sat Jun 26 04:42:42 UTC 2021 , Edited by admin on Sat Jun 26 04:42:42 UTC 2021
PRIMARY
MESH
D008376
Created by admin on Sat Jun 26 04:42:42 UTC 2021 , Edited by admin on Sat Jun 26 04:42:42 UTC 2021
PRIMARY
Related Record Type Details
BINDER->LIGAND
BINDING
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
METABOLIC ENZYME -> INHIBITOR
IC50
Related Record Type Details
METABOLITE -> PARENT
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC