MAPROTILINE

US Previously Marketed

Details

Stereochemistry	ACHIRAL
Molecular Formula	C20H23N
Molecular Weight	277.4033
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

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

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 191 Target ID: CHEMBL222 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17984940	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Dysthymic disorder 3 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf	Primary		Approved 8429	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
Major depressive disorder 173 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf	Primary		Approved 8429	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

C_max

Value	Dose	Co-administered	Analyte	Population
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
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

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 (starting) 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 Condition: depressive illness 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 (starting) 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 Condition: depressive illness Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf	unhealthy Health Status: unhealthy Condition: depressive illness Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf	unhealthy Health Status: unhealthy Condition: depressive illness Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf	unhealthy Health Status: unhealthy Condition: depressive illness Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf	unhealthy Health Status: unhealthy Condition: depressive illness Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf	unhealthy Health Status: unhealthy Condition: depressive illness Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf	unhealthy Health Status: unhealthy Condition: depressive illness Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf	unhealthy Health Status: unhealthy Condition: depressive illness Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf	unhealthy Health Status: unhealthy Condition: depressive illness Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf	unhealthy Health Status: unhealthy Condition: depressive illness Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf	unhealthy Health Status: unhealthy Condition: depressive illness Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf	unhealthy Health Status: unhealthy Condition: depressive illness Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf	unhealthy Health Status: unhealthy Condition: depressive illness Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf	unhealthy Health Status: unhealthy Condition: depressive illness Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/072285s021lbl.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737		substrate 1217	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP1A2 1054

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
Ca2+ channels 60	activator 214 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 1737	substrate 3367 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 1054	substrate 3367 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 1217	substrate 3367 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 1647	inhibitor 1626 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
BOC Sciences	136765-39-4	https://www.bocsci.com/maprotiline-d3-cas-136765-39-4-item-80161.html
BioSynth	J-000745	https://www.biosynth.com/en/products/all-products/products/J-000745.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
[Behavior pharmacology of maprotiline, a new antidepressant].	1975 Nov	1240830
The serotonin syndrome.	1992 Oct	1530086
Tianeptine: a review of its use in depressive disorders.	2001	11463130
[Psychiatric and psychological aspects of premenstrual syndrome].	2001 Nov-Dec	11865558
Semicarbazide-sensitive amine oxidase (SSAO) in the brain.	2002 Apr	11958526
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	12468041
The effects of tricyclic antidepressants on breast cancer risk.	2002 Jan 7	11857018
An investigation of monoamine receptors involved in antinociceptive effects of antidepressants.	2002 Jul	12088962
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	12076684
Antipsychotic, antidepressant, anxiolytic, and anticonvulsant drugs induce type II nitric oxide synthase mRNA in rat brain.	2002 Nov 29	12429386
Optimised procedures for the reversed-phase liquid chromatographic analysis of formulations containing tricyclic antidepressants.	2003 Apr 24	12852450
[11C]-DASB, a tool for in vivo measurement of SSRI-induced occupancy of the serotonin transporter: PET characterization and evaluation in cats.	2003 Feb	12454950
Tricyclic antidepressants as long-acting local anesthetics.	2003 May	12749958
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	14516488
[(11)C]PE2I: a highly selective radioligand for PET examination of the dopamine transporter in monkey and human brain.	2003 Sep	12811422
Frontotemporal arachnoid cyst connected to relapsing stupor.	2004 Winter	14990772
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
Analgesic therapy in postherpetic neuralgia: a quantitative systematic review.	2005 Jul	16013891
[Detection of maprotiline and proserine in forensic medical examination of cadaver].	2005 Mar-Apr	15881143
Inhibition of cardiac HERG potassium channels by antidepressant maprotiline.	2006 Feb 15	16423345
Dopamine release in human neocortical slices: characterization of inhibitory autoreceptors and of nicotinic acetylcholine receptor-evoked release.	2006 Jan 30	16377444
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	16499932

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

Name

Type

Language

MAPROTILINE

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 [INN]

Common Name

English

MAPROTILINE [MI]

Common Name

English

Maprotiline [WHO-DD]

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