MAPROTILINE HYDROCHLORIDE

US Previously Marketed

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 Search

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

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf

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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Norepinephrine transporter 197 Target ID: CHEMBL222 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17984940	Inhibitor 8504

Conditions

Condition	Modality	Targets	Highest Phase	Product
Dysthymic disorder 3 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf	Primary		Approved 8583	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
Major depressive disorder 179 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf	Primary		Approved 8583	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

C_max

Value	Dose	Co-administered	Analyte	Population
17.6 ng/mL DRUG LABEL https://pdf.hres.ca/dpd_pm/00014410.PDF	75 mg single, oral dose: 75 mg route of administration: Oral experiment type: SINGLE co-administered:		MAPROTILINE plasma	Homo sapiens
139 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/6775331	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

AUC

Value	Dose	Co-administered	Analyte	Population
3244 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/6775331	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
44.3 h DRUG LABEL https://pdf.hres.ca/dpd_pm/00014410.PDF	75 mg single, oral dose: 75 mg route of administration: Oral experiment type: SINGLE co-administered:		MAPROTILINE plasma	Homo sapiens

Doses

Dose	Population	Adverse events
75 mg 1 times / day multiple, oral Dose: 75 mg, 1 times / day Route: oral Route: multiple Dose: 75 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf	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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf

AEs

AE	Significance	Dose	Population
Drowsiness	16%	75 mg 1 times / day multiple, oral Dose: 75 mg, 1 times / day Route: oral Route: multiple Dose: 75 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf
Agitation	2%	75 mg 1 times / day multiple, oral Dose: 75 mg, 1 times / day Route: oral Route: multiple Dose: 75 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf
Insomnia	2%	75 mg 1 times / day multiple, oral Dose: 75 mg, 1 times / day Route: oral Route: multiple Dose: 75 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf
Nausea	2%	75 mg 1 times / day multiple, oral Dose: 75 mg, 1 times / day Route: oral Route: multiple Dose: 75 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf
Dry mouth	22%	75 mg 1 times / day multiple, oral Dose: 75 mg, 1 times / day Route: oral Route: multiple Dose: 75 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf
Anxiety	3%	75 mg 1 times / day multiple, oral Dose: 75 mg, 1 times / day Route: oral Route: multiple Dose: 75 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf
Tremor	3%	75 mg 1 times / day multiple, oral Dose: 75 mg, 1 times / day Route: oral Route: multiple Dose: 75 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf
Blurred vision	4%	75 mg 1 times / day multiple, oral Dose: 75 mg, 1 times / day Route: oral Route: multiple Dose: 75 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf
Fatigue	4%	75 mg 1 times / day multiple, oral Dose: 75 mg, 1 times / day Route: oral Route: multiple Dose: 75 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf
Headache	4%	75 mg 1 times / day multiple, oral Dose: 75 mg, 1 times / day Route: oral Route: multiple Dose: 75 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf
Weakness	4%	75 mg 1 times / day multiple, oral Dose: 75 mg, 1 times / day Route: oral Route: multiple Dose: 75 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf
Constipation	6%	75 mg 1 times / day multiple, oral Dose: 75 mg, 1 times / day Route: oral Route: multiple Dose: 75 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf
Nervousness	6%	75 mg 1 times / day multiple, oral Dose: 75 mg, 1 times / day Route: oral Route: multiple Dose: 75 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf
Dizziness	8%	75 mg 1 times / day multiple, oral Dose: 75 mg, 1 times / day Route: oral Route: multiple Dose: 75 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946		substrate 1388	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP1A2 1197

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
Ca2+ channels 62	activator 342 Sources: https://pubmed.ncbi.nlm.nih.gov/23219590/; https://pubmed.ncbi.nlm.nih.gov/15207657/	likely

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP3A4 1946	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12071336/	likely	likely (co-administration study) Comment: Relevant inhibition of the desmethylmaprotiline formation rate was observed in incubations with quinidine, furafylline and ketoconazole only Sources: https://pubmed.ncbi.nlm.nih.gov/12071336/
CYP1A2 1197	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12071336/	yes	likely (co-administration study) Comment: Relevant inhibition of the desmethylmaprotiline formation rate was observed in incubations with quinidine, furafylline and ketoconazole only Sources: https://pubmed.ncbi.nlm.nih.gov/12071336/
CYP2D6 1388	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12071336/	yes	likely (co-administration study) Comment: Relevant inhibition of the desmethylmaprotiline formation rate was observed in incubations with quinidine, furafylline and ketoconazole only Sources: https://pubmed.ncbi.nlm.nih.gov/12071336/

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://pubmed.ncbi.nlm.nih.gov/16423345/; https://pubmed.ncbi.nlm.nih.gov/16736158/

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY34088	https://www.001chemical.com/chem/10262-69-8
3B Scientific (Wuhan) Corp	3B2-6214	http://www.3bsc.com/index/pro_info.php?id=106789
AK Scientific, Inc. (AKSCI)	0643AA	http://www.aksci.com/item_detail.php?cat=0643AA
Alichem	229000247	http://www.alichem.com/en/products/10262-69-8.html
BioSynth	J-000745	https://www.biosynth.com/en/products/all-products/products/J-000745.html
BOC Sciences	136765-39-4	https://www.bocsci.com/maprotiline-d3-cas-136765-39-4-item-80161.html
Boerchem	BC204740	http://www.boerchem.com/?product_34465.html
ChemMol	30102260	http://www.chemmol.com/chemmol/30102260.html
ChemMol	44001931	http://www.chemmol.com/chemmol/44001931.html
Chemspace	CSSB00020590893	https://chem-space.com/CSSB00020590893
Clearsynth	CS-O-01861	https://www.clearsynth.com/en/CSO01861.html
Hairui	HR108004	http://www.hairuichem.com/en/product/10262-69-8.html
Molcore	MC34088	https://www.molcore.com/product/10262-69-8
OChem	14834	http://www.ocheminc.com/index.php?act=psearch&pid=262M698
Parchem	29339	http://www.parchem.com/chemical-supplier-distributor/Maprotiline-019339.aspx
Smolecule	S593121	https://www.smolecule.com/products/s593121
THE BioTek	bt-291925	https://www.thebiotek.com/product/others/bt-291925
Yuhao Chemical	YH21686	http://www.chemyuhao.com/10262-69-8.html

PubMed

Title	Date	PubMed
Increasing synaptic noradrenaline, serotonin and histamine enhances in vivo binding of phosphodiesterase-4 inhibitor (R)-[11C]rolipram in rat brain, lung and heart.	2006-06-20	16499932
Changes in AMPA subunit expression in the mouse brain after chronic treatment with the antidepressant maprotiline: a link between noradrenergic and glutamatergic function?	2006-04	16320045
Phosducin-like protein levels in leukocytes of patients with major depression and in rat cortex: the effect of chronic treatment with antidepressants.	2006-03-30	16510194
Age-dependent interactive changes in serotonergic and noradrenergic cortical axon terminals in F344 rats.	2006-03	16406149
Inhibition of cardiac HERG potassium channels by antidepressant maprotiline.	2006-02-15	16423345
A fully automated turbulent-flow liquid chromatography-tandem mass spectrometry technique for monitoring antidepressants in human serum.	2006-02	16418706
Dopamine release in human neocortical slices: characterization of inhibitory autoreceptors and of nicotinic acetylcholine receptor-evoked release.	2006-01-30	16377444
Are the effects of the antidepressants amitriptyline, maprotiline, and fluoxetine on inhibitory avoidance state-dependent?	2006-01-06	16159672
Development of a solid phase extraction for 13 'new' generation antidepressants and their active metabolites for gas chromatographic-mass spectrometric analysis.	2005-12-09	16314157
[(11)C]MADAM, a new serotonin transporter radioligand characterized in the monkey brain by PET.	2005-12-01	16138320
Reduction of Submissive Behavior Model for antidepressant drug activity testing: study using a video-tracking system.	2005-12	16286818
Citalopram associated with acute angle-closure glaucoma: case report.	2005-10-04	16202173
[Evaluation of antidepressant activity in a model of depressionlike state due to social isolation in rats].	2005-10-01	16193649
Synthesis and C-11 labeling of three potent norepinephrine transporter selective ligands ((R)-nisoxetine, lortalamine, and oxaprotiline) for comparative PET studies in baboons.	2005-08-01	15914010
Screening antidepressants in the chick separation-stress paradigm.	2005-08	15778882
Internet-based search of randomised trials relevant to mental health originating in the Arab world.	2005-07-26	16045805
Analgesic therapy in postherpetic neuralgia: a quantitative systematic review.	2005-07	16013891
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.	2005-07	15998285
Effect of long-term administration of antidepressants on the lipid composition of brain plasma membranes.	2005-06	16118474
[Detection of maprotiline and proserine in forensic medical examination of cadaver].	2005-05-11	15881143
The monoamine-mediated antiallodynic effects of intrathecally administered milnacipran, a serotonin noradrenaline reuptake inhibitor, in a rat model of neuropathic pain.	2005-05	15845695
Effect of pharmacologically selective antidepressants on serotonin uptake in rat platelets.	2005-03	15900091
Contribution of sleep research to the development of new antidepressants.	2005	16416706
Dose-response relationship of recent antidepressants in the short-term treatment of depression.	2005	16156383
The AGNP-TDM Expert Group Consensus Guidelines: focus on therapeutic monitoring of antidepressants.	2005	16156382
Is dopamine a limiting factor of the antidepressant-like effect in the mouse forced swimming test?	2004-12	15588751
Serotonin syndrome due to association of venlafaxine, maprotiline and reboxetine.	2004-11	15504661
Risk of fetal exposure to tricyclic antidepressants.	2004-10	15507199
Serotonin and noradrenaline reuptake inhibitors in animal models of pain.	2004-10	15378668
Inhibition of G protein-activated inwardly rectifying K+ channels by various antidepressant drugs.	2004-10	15150531
Tricyclic antidepressants, QT interval prolongation, and torsade de pointes.	2004-09-04	15345781
Clinical study on electro-acupuncture treatment for 30 cases of mental depression.	2004-09	15510791
Effect of the antidepressant maprotiline on calcium movement and the viability of renal tubular cells.	2004-08	15057508
Effect of maprotiline on Ca(2+) movement in human neuroblastoma cells.	2004-07-16	15207657
Effect of the antidepressant maprotiline on Ca2+ movement and proliferation in human prostate cancer cells.	2004-07	15236632
[Determination of amitriptyline and maprotiline in health foods by GC-MS].	2004-05	15712928
[Comparative observation on efficacy of jieyu pill and maprotiline in treating depression].	2004-05	15199625
Human liver aldehyde oxidase: inhibition by 239 drugs.	2004-01	14681337
[Placebo to antidepressant effects ratio by electroencephalographic data].	2004	15581036
Current use of selective serotonin reuptake inhibitors and risk of acute myocardial infarction.	2004	15554748
Increased subcutaneous abdominal tissue norepinephrine levels in patients with anorexia nervosa: an in vivo microdialysis study.	2004	15312000
Frontotemporal arachnoid cyst connected to relapsing stupor.	2004	14990772
In vivo measurement of the serotonin transporter with (S)-([18F]fluoromethyl)-(+)-McN5652.	2003-11	12931143
Effects of some antidepressant drugs on tryptaminergic responses of the rat jejunum.	2003-10	12928582
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.	2003-09	14516488
Analysis of eighteen antidepressants, four atypical antipsychotics and active metabolites in serum by liquid chromatography: a simple tool for therapeutic drug monitoring.	2003-08-25	12888196
The promises and pitfalls of reboxetine.	2003	14647527
[Current views on migraine and anti-migraine preparations].	2003	14598505
The serotonin syndrome.	1992-10	1530086
Severe mania after maprotiline-induced coma.	1992-07	1528960

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

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 `Mon Mar 31 17:46:23 GMT 2025` Edited by `admin` on `Mon Mar 31 17:46:23 GMT 2025`
Record UNII	7C8J54PVFI
Record Status	`Validated (UNII)`
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Name

Type

Language

MAPROTILINE HYDROCHLORIDE

Common Name

English

LUDIOMIL

Preferred 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

9,10-ETHANOANTHRACENE-9(10H)-PROPANAMINE, N-METHYL-, HYDROCHLORIDE

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C94727