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

Details

Stereochemistry ACHIRAL
Molecular Formula C20H23N.CH4O3S
Molecular Weight 373.509
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of MAPROTILINE MESYLATE

SMILES

CS(O)(=O)=O.CNCCCC12CCC(C3=CC=CC=C13)C4=CC=CC=C24

InChI

InChIKey=IUOFVKUAHKGVIO-UHFFFAOYSA-N
InChI=1S/C20H23N.CH4O3S/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;1-5(2,3)4/h2-5,7-10,15,21H,6,11-14H2,1H3;1H3,(H,2,3,4)

HIDE SMILES / InChI

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

Molecular Formula CH4O3S
Molecular Weight 96.106
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
[Behavior pharmacology of maprotiline, a new antidepressant].
1975 Nov
The serotonin syndrome.
1992 Oct
The anxiolytic-like effect of MCI-225, a selective NA reuptake inhibitor with 5-HT3 receptor antagonism.
2001 Apr
Modeling panic attacks.
2001 Dec
[QT prolongation and torsade de pointes tachycardia during therapy with maprotiline. Differential diagnostic and therapeutic aspects].
2001 Dec 7
[Psychiatric and psychological aspects of premenstrual syndrome].
2001 Nov-Dec
Mood disorders in patients with epilepsy: epidemiology and management.
2002
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
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
Imipramine, mianserine and maprotiline block delayed rectifier potassium current in ventricular myocytes.
2002 Feb
Increased plasma concentration of maprotiline by coadministration of risperidone.
2002 Feb
The effects of tricyclic antidepressants on breast cancer risk.
2002 Jan 7
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
[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
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
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
Olanzapine in the treatment-resistant, combat-related PTSD--a series of case reports.
2003 May
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
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
Effect of the antidepressant maprotiline on calcium movement and the viability of renal tubular cells.
2004 Aug
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
Clinical study on electro-acupuncture treatment for 30 cases of mental depression.
2004 Sep
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
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
[(11)C]MADAM, a new serotonin transporter radioligand characterized in the monkey brain by PET.
2005 Dec 1
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
Effect of long-term administration of antidepressants on the lipid composition of brain plasma membranes.
2005 Jun
Effect of pharmacologically selective antidepressants on serotonin uptake in rat platelets.
2005 Mar
[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
Inhibition of cardiac HERG potassium channels by antidepressant maprotiline.
2006 Feb 15
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 Thu Jul 06 02:05:05 UTC 2023
Edited
by admin
on Thu Jul 06 02:05:05 UTC 2023
Record UNII
22P65W41V0
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
MAPROTILINE MESYLATE
Common Name English
Maprotiline mesilate [WHO-DD]
Common Name English
MAPROTILINE MESILATE
WHO-DD  
Common Name English
Code System Code Type Description
FDA UNII
22P65W41V0
Created by admin on Thu Jul 06 02:05:05 UTC 2023 , Edited by admin on Thu Jul 06 02:05:05 UTC 2023
PRIMARY
ECHA (EC/EINECS)
261-488-0
Created by admin on Thu Jul 06 02:05:05 UTC 2023 , Edited by admin on Thu Jul 06 02:05:05 UTC 2023
PRIMARY
RXCUI
236328
Created by admin on Thu Jul 06 02:05:05 UTC 2023 , Edited by admin on Thu Jul 06 02:05:05 UTC 2023
PRIMARY RxNorm
EVMPD
SUB03089MIG
Created by admin on Thu Jul 06 02:05:05 UTC 2023 , Edited by admin on Thu Jul 06 02:05:05 UTC 2023
PRIMARY
PUBCHEM
198375
Created by admin on Thu Jul 06 02:05:05 UTC 2023 , Edited by admin on Thu Jul 06 02:05:05 UTC 2023
PRIMARY
EPA CompTox
DTXSID30207646
Created by admin on Thu Jul 06 02:05:05 UTC 2023 , Edited by admin on Thu Jul 06 02:05:05 UTC 2023
PRIMARY
SMS_ID
100000085389
Created by admin on Thu Jul 06 02:05:05 UTC 2023 , Edited by admin on Thu Jul 06 02:05:05 UTC 2023
PRIMARY
CAS
58902-67-3
Created by admin on Thu Jul 06 02:05:05 UTC 2023 , Edited by admin on Thu Jul 06 02:05:05 UTC 2023
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
PARENT -> SALT/SOLVATE
Related Record Type Details
ACTIVE MOIETY