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

Details

Stereochemistry ACHIRAL
Molecular Formula C20H23N.ClH
Molecular Weight 313.864
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of MAPROTILINE HYDROCHLORIDE

SMILES

Cl.CNCCCC12CCC(C3=CC=CC=C13)C4=CC=CC=C24

InChI

InChIKey=NZDMFGKECODQRY-UHFFFAOYSA-N
InChI=1S/C20H23N.ClH/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;1H

HIDE SMILES / InChI

Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C20H23N
Molecular Weight 277.4033
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
Severe mania after maprotiline-induced coma.
1992 Jul
Tianeptine: a review of its use in depressive disorders.
2001
The anxiolytic-like effect of MCI-225, a selective NA reuptake inhibitor with 5-HT3 receptor antagonism.
2001 Apr
Involvement of 5-HT(2C) receptors in the anti-immobility effects of antidepressants in the forced swimming test in mice.
2001 Apr
[Tricyclic antidepressant, tetracyclic antidepressant].
2001 Aug
Low frequency rTMS as an add-on antidepressive strategy: heterogeneous impact on 99mTc-HMPAO and 18 F-FDG uptake as measured simultaneously with the double isotope SPECT technique. Pilot study.
2001 Aug
[QT prolongation and torsade de pointes tachycardia during therapy with maprotiline. Differential diagnostic and therapeutic aspects].
2001 Dec 7
Gender differences in the efficacy of fluoxetine and maprotiline in depressed patients: a double-blind trial of antidepressants with serotonergic or norepinephrinergic reuptake inhibition profile.
2001 Jun
Venlafaxine withdrawal syndrome not prevented by maprotiline, but resolved by sertraline.
2001 Mar
Discriminative stimulus properties of the selective norepinephrine reuptake inhibitor, reboxetine, in rats.
2001 Nov
Mood disorders in patients with epilepsy: epidemiology and management.
2002
Synthesis of a fluorine-18-labelled derivative of 6-nitroquipazine, as a radioligand for the in vivo serotonin transporter imaging with PET.
2002 Aug
Combination of clozapine and maprotiline in refractory psychotic depression.
2002 Dec
Simultaneous quantification of citalopram, clozapine, fluoxetine, norfluoxetine, maprotiline, desmethylmaprotiline and trazodone in human serum by HPLC analysis.
2002 Dec
Differential effects of the 5-HT2 receptor antagonist on the anti-immobility effects of noradrenaline and serotonin reuptake inhibitors in the forced swimming test.
2002 Dec 20
[Comparative study of electro-acupuncture and maprotiline in treating depression].
2002 Jul
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
7,7,8,8-Tetracyanoquinodimethane as a new derivatization reagent for high-performance liquid chromatography and thin-layer chromatography: rapid screening of plasma for some antidepressants.
2002 Jul 15
Cytochrome P450 enzymes contributing to demethylation of maprotiline in man.
2002 Mar
[Tolerability and efficacy of combined antidepressant therapy].
2002 Mar-Apr
[QT prolongation and torsade de pointes--tachycardia in therapy with maprotiline].
2002 May 3
Antipsychotic, antidepressant, anxiolytic, and anticonvulsant drugs induce type II nitric oxide synthase mRNA in rat brain.
2002 Nov 29
[Depression in epilepsy: symptom or syndrome?].
2002 Nov-Dec
[Current views on migraine and anti-migraine preparations].
2003
Optimised procedures for the reversed-phase liquid chromatographic analysis of formulations containing tricyclic antidepressants.
2003 Apr 24
Analysis of eighteen antidepressants, four atypical antipsychotics and active metabolites in serum by liquid chromatography: a simple tool for therapeutic drug monitoring.
2003 Aug 25
Differential effects of K(ATP) channel blockers on [(3)H]-noradrenaline overflow after short- and long-term exposure to (+)-oxaprotiline or desipramine.
2003 Feb
[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 inhibition of the norepinephrine transporter in the brain participates in seizure sensitization to cocaine and local anesthetics.
2003 Feb 21
Chronic treatment with antidepressants decreases intraoperative core hypothermia.
2003 Jul
Bi-phasic change in BDNF gene expression following antidepressant drug treatment.
2003 Jun
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
[(11)C]PE2I: a highly selective radioligand for PET examination of the dopamine transporter in monkey and human brain.
2003 Sep
The promises and pitfalls of reboxetine.
2003 Winter
Increased subcutaneous abdominal tissue norepinephrine levels in patients with anorexia nervosa: an in vivo microdialysis study.
2004
Is dopamine a limiting factor of the antidepressant-like effect in the mouse forced swimming test?
2004 Dec
Human liver aldehyde oxidase: inhibition by 239 drugs.
2004 Jan
Effect of maprotiline on Ca(2+) movement in human neuroblastoma cells.
2004 Jul 16
[Determination of amitriptyline and maprotiline in health foods by GC-MS].
2004 May
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
Synthesis and C-11 labeling of three potent norepinephrine transporter selective ligands ((R)-nisoxetine, lortalamine, and oxaprotiline) for comparative PET studies in baboons.
2005 Aug 1
Reduction of Submissive Behavior Model for antidepressant drug activity testing: study using a video-tracking system.
2005 Dec
Internet-based search of randomised trials relevant to mental health originating in the Arab world.
2005 Jul 26
Are the effects of the antidepressants amitriptyline, maprotiline, and fluoxetine on inhibitory avoidance state-dependent?
2006 Jan 6
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 Wed Jul 05 22:37:52 UTC 2023
Edited
by admin
on Wed Jul 05 22:37:52 UTC 2023
Record UNII
7C8J54PVFI
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
MAPROTILINE HYDROCHLORIDE
EP   MART.   MI   ORANGE BOOK   USP   USP-RS   VANDF   WHO-DD  
Common Name English
MAPROTILINE HYDROCHLORIDE [ORANGE BOOK]
Common Name English
MAPROTILINE HYDROCHLORIDE [MART.]
Common Name English
MAPROTILINE HYDROCHLORIDE [VANDF]
Common Name English
MAPROTILINE HYDROCHLORIDE [MI]
Common Name English
NSC-757085
Code English
MAPROTILINE HYDROCHLORIDE [EP MONOGRAPH]
Common Name English
BA-34276 HYDROCHLORIDE
Code English
MAPROTILINE HYDROCHLORIDE [JAN]
Common Name English
BA-34,276
Code English
MAPROTILINE HCL
Common Name English
Maprotiline hydrochloride [WHO-DD]
Common Name English
N-Methyl-9,10-ethanoanthracene-9(10H)-propylamine hydrochloride
Systematic Name English
BA-34276
Code English
MAPROTILINE HYDROCHLORIDE [USP-RS]
Common Name English
MAPROTILINE HYDROCHLORIDE [USP MONOGRAPH]
Common Name English
LUDIOMIL
Brand Name English
9,10-ETHANOANTHRACENE-9(10H)-PROPANAMINE, N-METHYL-, HYDROCHLORIDE
Systematic Name English
Classification Tree Code System Code
NCI_THESAURUS C94727
Created by admin on Wed Jul 05 22:37:52 UTC 2023 , Edited by admin on Wed Jul 05 22:37:52 UTC 2023
Code System Code Type Description
MERCK INDEX
M7083
Created by admin on Wed Jul 05 22:37:52 UTC 2023 , Edited by admin on Wed Jul 05 22:37:52 UTC 2023
PRIMARY Merck Index
RS_ITEM_NUM
1375207
Created by admin on Wed Jul 05 22:37:52 UTC 2023 , Edited by admin on Wed Jul 05 22:37:52 UTC 2023
PRIMARY
FDA UNII
7C8J54PVFI
Created by admin on Wed Jul 05 22:37:52 UTC 2023 , Edited by admin on Wed Jul 05 22:37:52 UTC 2023
PRIMARY
ChEMBL
CHEMBL21731
Created by admin on Wed Jul 05 22:37:52 UTC 2023 , Edited by admin on Wed Jul 05 22:37:52 UTC 2023
PRIMARY
CAS
10347-81-6
Created by admin on Wed Jul 05 22:37:52 UTC 2023 , Edited by admin on Wed Jul 05 22:37:52 UTC 2023
PRIMARY
NSC
757085
Created by admin on Wed Jul 05 22:37:52 UTC 2023 , Edited by admin on Wed Jul 05 22:37:52 UTC 2023
PRIMARY
EPA CompTox
DTXSID2044507
Created by admin on Wed Jul 05 22:37:52 UTC 2023 , Edited by admin on Wed Jul 05 22:37:52 UTC 2023
PRIMARY
NCI_THESAURUS
C47594
Created by admin on Wed Jul 05 22:37:52 UTC 2023 , Edited by admin on Wed Jul 05 22:37:52 UTC 2023
PRIMARY
SMS_ID
100000092398
Created by admin on Wed Jul 05 22:37:52 UTC 2023 , Edited by admin on Wed Jul 05 22:37:52 UTC 2023
PRIMARY
DRUG BANK
DBSALT000482
Created by admin on Wed Jul 05 22:37:52 UTC 2023 , Edited by admin on Wed Jul 05 22:37:52 UTC 2023
PRIMARY
RXCUI
203126
Created by admin on Wed Jul 05 22:37:52 UTC 2023 , Edited by admin on Wed Jul 05 22:37:52 UTC 2023
PRIMARY RxNorm
EVMPD
SUB03088MIG
Created by admin on Wed Jul 05 22:37:52 UTC 2023 , Edited by admin on Wed Jul 05 22:37:52 UTC 2023
PRIMARY
PUBCHEM
71478
Created by admin on Wed Jul 05 22:37:52 UTC 2023 , Edited by admin on Wed Jul 05 22:37:52 UTC 2023
PRIMARY
ECHA (EC/EINECS)
233-758-8
Created by admin on Wed Jul 05 22:37:52 UTC 2023 , Edited by admin on Wed Jul 05 22:37:52 UTC 2023
PRIMARY
Related Record Type Details
BASIS OF STRENGTH->SUBSTANCE
ASSAY (TITRATION)
EP
BASIS OF STRENGTH->SUBSTANCE
ASSAY (TITRATION)
USP
PARENT -> SALT/SOLVATE
Related Record Type Details
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
Related Record Type Details
ACTIVE MOIETY