MAPROTILINE MESYLATE

US Previously Marketed

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 Search

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

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 1988
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 1988

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
Severe mania after maprotiline-induced coma.	1992 Jul	1528960
Bilateral angle closure glaucoma and visual loss precipitated by antidepressant and antianxiety agents in a patient with depression.	2000 Sep-Oct	10965252
Involvement of 5-HT(2C) receptors in the anti-immobility effects of antidepressants in the forced swimming test in mice.	2001 Apr	11313160
[Tricyclic antidepressant, tetracyclic antidepressant].	2001 Aug	11519150
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	11473205
[QT prolongation and torsade de pointes tachycardia during therapy with maprotiline. Differential diagnostic and therapeutic aspects].	2001 Dec 7	11740632
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	11418283
Antipsychotic, antidepressant, anxiolytic, and anticonvulsant drugs induce type II nitric oxide synthase mRNA in rat brain.	2002 Nov 29	12429386
[Effects of escitalopram on anxiety symptoms in depression].	2002 Sep-Oct	12386549
Chronic inhibition of the norepinephrine transporter in the brain participates in seizure sensitization to cocaine and local anesthetics.	2003 Feb 21	12573515
Chronic treatment with antidepressants decreases intraoperative core hypothermia.	2003 Jul	12818981
Olanzapine in the treatment-resistant, combat-related PTSD--a series of case reports.	2003 May	12752037
Tricyclic antidepressants as long-acting local anesthetics.	2003 May	12749958
[(11)C]PE2I: a highly selective radioligand for PET examination of the dopamine transporter in monkey and human brain.	2003 Sep	12811422
Increased subcutaneous abdominal tissue norepinephrine levels in patients with anorexia nervosa: an in vivo microdialysis study.	2004	15312000
Tricyclic antidepressants, QT interval prolongation, and torsade de pointes.	2004 Sep-Oct	15345781
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
Screening antidepressants in the chick separation-stress paradigm.	2005 Aug	15778882
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	15914010
[Evaluation of antidepressant activity in a model of depressionlike state due to social isolation in rats].	2005 Jul-Aug	16193649
Citalopram associated with acute angle-closure glaucoma: case report.	2005 Oct 4	16202173
Are the effects of the antidepressants amitriptyline, maprotiline, and fluoxetine on inhibitory avoidance state-dependent?	2006 Jan 6	16159672

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 `Fri Dec 15 18:55:02 GMT 2023` Edited by `admin` on `Fri Dec 15 18:55:02 GMT 2023`
Record UNII	22P65W41V0
Record Status	`Validated (UNII)`
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Name

Type

Language

MAPROTILINE MESYLATE

Common Name

English

Maprotiline mesilate [WHO-DD]

Common Name

English

MAPROTILINE MESILATE

Common Name

English

Code System Code Type Description

FDA UNII

22P65W41V0