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

1988
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

1988
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
Maprotiline hydrochloride and grand-mal seizures.
1978 Sep 30
Severe mania after maprotiline-induced coma.
1992 Jul
The serotonin syndrome.
1992 Oct
Bilateral angle closure glaucoma and visual loss precipitated by antidepressant and antianxiety agents in a patient with depression.
2000 Sep-Oct
The anxiolytic-like effect of MCI-225, a selective NA reuptake inhibitor with 5-HT3 receptor antagonism.
2001 Apr
Venlafaxine withdrawal syndrome not prevented by maprotiline, but resolved by sertraline.
2001 Mar
[Psychiatric and psychological aspects of premenstrual syndrome].
2001 Nov-Dec
Effects of psychotropic drugs on seizure threshold.
2002
Semicarbazide-sensitive amine oxidase (SSAO) in the brain.
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
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
[Tolerability and efficacy of combined antidepressant therapy].
2002 Mar-Apr
[QT prolongation and torsade de pointes--tachycardia in therapy with maprotiline].
2002 May 3
[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
Differential effects of antidepressants on glucocorticoid receptors in human primary blood cells and human monocytic U-937 cells.
2003 Apr
Optimised procedures for the reversed-phase liquid chromatographic analysis of formulations containing tricyclic antidepressants.
2003 Apr 24
Chronic treatment with antidepressants decreases intraoperative core hypothermia.
2003 Jul
Bi-phasic change in BDNF gene expression following antidepressant drug treatment.
2003 Jun
Tricyclic antidepressants as long-acting local anesthetics.
2003 May
[(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
[Placebo to antidepressant effects ratio by electroencephalographic data].
2004
Current use of selective serotonin reuptake inhibitors and risk of acute myocardial infarction.
2004
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
[Determination of amitriptyline and maprotiline in health foods by GC-MS].
2004 May
[Comparative observation on efficacy of jieyu pill and maprotiline in treating depression].
2004 May
Serotonin syndrome due to association of venlafaxine, maprotiline and reboxetine.
2004 Nov
Risk of fetal exposure to tricyclic antidepressants.
2004 Oct
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
Screening antidepressants in the chick separation-stress paradigm.
2005 Aug
Reduction of Submissive Behavior Model for antidepressant drug activity testing: study using a video-tracking system.
2005 Dec
Analgesic therapy in postherpetic neuralgia: a quantitative systematic review.
2005 Jul
[Evaluation of antidepressant activity in a model of depressionlike state due to social isolation in rats].
2005 Jul-Aug
[Detection of maprotiline and proserine in forensic medical examination of cadaver].
2005 Mar-Apr
The monoamine-mediated antiallodynic effects of intrathecally administered milnacipran, a serotonin noradrenaline reuptake inhibitor, in a rat model of neuropathic pain.
2005 May
A fully automated turbulent-flow liquid chromatography-tandem mass spectrometry technique for monitoring antidepressants in human serum.
2006 Feb
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 Fri Dec 15 15:05:54 GMT 2023
Edited
by admin
on Fri Dec 15 15:05:54 GMT 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 Fri Dec 15 15:05:54 GMT 2023 , Edited by admin on Fri Dec 15 15:05:54 GMT 2023
Code System Code Type Description
MERCK INDEX
m7083
Created by admin on Fri Dec 15 15:05:54 GMT 2023 , Edited by admin on Fri Dec 15 15:05:54 GMT 2023
PRIMARY Merck Index
RS_ITEM_NUM
1375207
Created by admin on Fri Dec 15 15:05:54 GMT 2023 , Edited by admin on Fri Dec 15 15:05:54 GMT 2023
PRIMARY
FDA UNII
7C8J54PVFI
Created by admin on Fri Dec 15 15:05:54 GMT 2023 , Edited by admin on Fri Dec 15 15:05:54 GMT 2023
PRIMARY
ChEMBL
CHEMBL21731
Created by admin on Fri Dec 15 15:05:54 GMT 2023 , Edited by admin on Fri Dec 15 15:05:54 GMT 2023
PRIMARY
CAS
10347-81-6
Created by admin on Fri Dec 15 15:05:54 GMT 2023 , Edited by admin on Fri Dec 15 15:05:54 GMT 2023
PRIMARY
NSC
757085
Created by admin on Fri Dec 15 15:05:54 GMT 2023 , Edited by admin on Fri Dec 15 15:05:54 GMT 2023
PRIMARY
EPA CompTox
DTXSID2044507
Created by admin on Fri Dec 15 15:05:54 GMT 2023 , Edited by admin on Fri Dec 15 15:05:54 GMT 2023
PRIMARY
NCI_THESAURUS
C47594
Created by admin on Fri Dec 15 15:05:54 GMT 2023 , Edited by admin on Fri Dec 15 15:05:54 GMT 2023
PRIMARY
SMS_ID
100000092398
Created by admin on Fri Dec 15 15:05:54 GMT 2023 , Edited by admin on Fri Dec 15 15:05:54 GMT 2023
PRIMARY
DRUG BANK
DBSALT000482
Created by admin on Fri Dec 15 15:05:54 GMT 2023 , Edited by admin on Fri Dec 15 15:05:54 GMT 2023
PRIMARY
RXCUI
203126
Created by admin on Fri Dec 15 15:05:54 GMT 2023 , Edited by admin on Fri Dec 15 15:05:54 GMT 2023
PRIMARY RxNorm
EVMPD
SUB03088MIG
Created by admin on Fri Dec 15 15:05:54 GMT 2023 , Edited by admin on Fri Dec 15 15:05:54 GMT 2023
PRIMARY
PUBCHEM
71478
Created by admin on Fri Dec 15 15:05:54 GMT 2023 , Edited by admin on Fri Dec 15 15:05:54 GMT 2023
PRIMARY
ECHA (EC/EINECS)
233-758-8
Created by admin on Fri Dec 15 15:05:54 GMT 2023 , Edited by admin on Fri Dec 15 15:05:54 GMT 2023
PRIMARY
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