LOFEPRAMINE

Possibly Marketed Outside US

Details

Stereochemistry	ACHIRAL
Molecular Formula	C26H27ClN2O
Molecular Weight	418.958
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN(CCCN1C2=CC=CC=C2CCC3=CC=CC=C13)CC(=O)C4=CC=C(Cl)C=C4

InChI

InChIKey=SAPNXPWPAUFAJU-UHFFFAOYSA-N

InChI=1S/C26H27ClN2O/c1-28(19-26(30)22-13-15-23(27)16-14-22)17-6-18-29-24-9-4-2-7-20(24)11-12-21-8-3-5-10-25(21)29/h2-5,7-10,13-16H,6,11-12,17-19H2,1H3

HIDE SMILES / InChI

Molecular Formula	C26H27ClN2O
Molecular Weight	418.958
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.medicines.org.uk/emc/PIL.28069.latest.pdf | https://www.ncbi.nlm.nih.gov/pubmed/2649353 | http://cdn.neiglobal.com/content/pg/live/lofepramine.pdf | https://www.ncbi.nlm.nih.gov/pubmed/2891742

Lofepramine is a tricyclic antidepressant that is structurally similar to imipramine and is extensively metabolised to desipramine. In the absence of other major pharmacological effects it appears that its antidepressant activity stems from the facilitation of noradrenergic neurotransmission by uptake inhibition, and possibly by the additional facilitation of serotoninergic neurotransmission. The overall therapeutic efficacy of lofepramine is comparable to that of imipramine, amitriptyline, clomipramine, maprotiline and mianserin in patients with depression of varying severity, and coexisting anxiety. Lofepramine is a strong inhibitor of norepinephrine reuptake (Ki=5.4 nM) and a moderate inhibitor of serotonin reuptake (Ki=70 nM). It is a weak-intermediate level antagonist of the muscarinic acetylcholine receptors.Lofepramine is licensed for the treatment of depression in the United Kingdom.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
norepinephrine uptake 18 Target ID: GO:0051620 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2891742 \| https://www.ncbi.nlm.nih.gov/pubmed/8445992 \| https://www.ncbi.nlm.nih.gov/pubmed/15076 \| https://www.ncbi.nlm.nih.gov/pubmed/971713	Inhibitor 8504	4.5 nM [IC50]
Serotonin transporter 183 Target ID: CHEMBL228 Sources: http://www.genome.jp/dbget-bin/www_bget?D08140 \| https://www.google.com/patents/US20120115149	Inhibitor 8504	7.15 null [pKi]
Norepinephrine transporter 197 Target ID: CHEMBL222 Sources: http://www.genome.jp/dbget-bin/www_bget?D08140 \| https://www.ncbi.nlm.nih.gov/pubmed/15076	Inhibitor 8504	8.27 null [pKi]
Muscarinic acetylcholine receptor 162 Target ID: CHEMBL2094109 Sources: https://www.ncbi.nlm.nih.gov/pubmed/3094050	Antagonist 2849	285.0 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Depression 240 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15876362 https://www.ncbi.nlm.nih.gov/pubmed/8794599	Primary		Approved 8583	Lofepramine Approved Use Lofepramine Tablets are used to treat the symptoms of depression. Common symptoms include feelings of worthlessness or deep sadness, difficulty with everyday tasks, sleeping too much or not being able to sleep, and feeling anxious.

C_max

Value	Dose	Analyte	Population
22.9 ng/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/2/430574_1174004F1028_2_A12_1F.pdf#page=17 \| https://www.jstage.jst.go.jp/article/jscpt1970/7/2/7_2_161/_article/-char/en	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	LOFEPRAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
9.8 ng/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/2/430574_1174004F1028_2_A12_1F.pdf#page=17 \| https://www.jstage.jst.go.jp/article/jscpt1970/7/2/7_2_161/_article/-char/en	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	DESIPRAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
30 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2677125/	70 mg single, oral dose: 70 mg route of administration: Oral experiment type: SINGLE co-administered:	LOFEPRAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
50 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2677125/	105 mg single, oral dose: 105 mg route of administration: Oral experiment type: SINGLE co-administered:	LOFEPRAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
50 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2677125/	140 mg single, oral dose: 140 mg route of administration: Oral experiment type: SINGLE co-administered:	LOFEPRAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
46 μg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2677125/	70 mg single, oral dose: 70 mg route of administration: Oral experiment type: SINGLE co-administered:	LOFEPRAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
113 μg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2677125/	105 mg single, oral dose: 105 mg route of administration: Oral experiment type: SINGLE co-administered:	LOFEPRAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
128 μg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2677125/	140 mg single, oral dose: 140 mg route of administration: Oral experiment type: SINGLE co-administered:	LOFEPRAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
2.7 h OTHER GOV'T https://www.info.pmda.go.jp/go/interview/2/430574_1174004F1028_2_A12_1F.pdf#page=17 \| https://www.jstage.jst.go.jp/article/jscpt1970/7/2/7_2_161/_article/-char/en	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	LOFEPRAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
3.4 h OTHER GOV'T https://www.info.pmda.go.jp/go/interview/2/430574_1174004F1028_2_A12_1F.pdf#page=17 \| https://www.jstage.jst.go.jp/article/jscpt1970/7/2/7_2_161/_article/-char/en	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	DESIPRAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
1.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2677125/	70 mg single, oral dose: 70 mg route of administration: Oral experiment type: SINGLE co-administered:	LOFEPRAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2677125/	105 mg single, oral dose: 105 mg route of administration: Oral experiment type: SINGLE co-administered:	LOFEPRAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2677125/	140 mg single, oral dose: 140 mg route of administration: Oral experiment type: SINGLE co-administered:	LOFEPRAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
0.7% OTHER GOV'T https://www.info.pmda.go.jp/go/interview/2/430574_1174004F1028_2_A12_1F.pdf#page=18			LOFEPRAMINE plasma	Homo sapiens
1% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/848046/			LOFEPRAMINE plasma	Homo sapiens

Doses

Dose	Population	Adverse events
3.36 g single, oral Overdose Dose: 3.36 g Route: oral Route: single Dose: 3.36 g Sources: https://pubmed.ncbi.nlm.nih.gov/2408087/	unknown, ADULT Health Status: unknown Age Group: ADULT Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/2408087/	Disc. AE: Dry mouth, Dilated pupils... AEs leading to discontinuation/dose reduction: Dry mouth Dilated pupils Ileus Sources: https://pubmed.ncbi.nlm.nih.gov/2408087/
3.78 g single, oral Overdose Dose: 3.78 g Route: oral Route: single Dose: 3.78 g Sources: https://pubmed.ncbi.nlm.nih.gov/2408087/	unknown, ADULT Health Status: unknown Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/2408087/	Disc. AE: Dizziness, Dilated pupils... AEs leading to discontinuation/dose reduction: Dizziness Dilated pupils Sources: https://pubmed.ncbi.nlm.nih.gov/2408087/
4.9 g single, oral Overdose Dose: 4.9 g Route: oral Route: single Dose: 4.9 g Sources: https://pubmed.ncbi.nlm.nih.gov/2408087/	unknown, ADULT Health Status: unknown Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/2408087/	Disc. AE: Tachycardia... AEs leading to discontinuation/dose reduction: Tachycardia Sources: https://pubmed.ncbi.nlm.nih.gov/2408087/
210 mg 1 times / day multiple, oral Recommended Dose: 210 mg, 1 times / day Route: oral Route: multiple Dose: 210 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/395129/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/395129/	Other AEs: Dry mouth, Giddiness... Other AEs: Dry mouth (9%) Giddiness (9%) Sources: https://pubmed.ncbi.nlm.nih.gov/395129/
70 mg 3 times / day multiple, oral Recommended Dose: 70 mg, 3 times / day Route: oral Route: multiple Dose: 70 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/320827/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/320827/	Disc. AE: Palpitation... AEs leading to discontinuation/dose reduction: Palpitation (6.5%) Sources: https://pubmed.ncbi.nlm.nih.gov/320827/

AEs

AE	Significance	Dose	Population
Dilated pupils	Disc. AE	3.36 g single, oral Overdose Dose: 3.36 g Route: oral Route: single Dose: 3.36 g Sources: https://pubmed.ncbi.nlm.nih.gov/2408087/	unknown, ADULT Health Status: unknown Age Group: ADULT Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/2408087/
Dry mouth	Disc. AE	3.36 g single, oral Overdose Dose: 3.36 g Route: oral Route: single Dose: 3.36 g Sources: https://pubmed.ncbi.nlm.nih.gov/2408087/	unknown, ADULT Health Status: unknown Age Group: ADULT Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/2408087/
Ileus	Disc. AE	3.36 g single, oral Overdose Dose: 3.36 g Route: oral Route: single Dose: 3.36 g Sources: https://pubmed.ncbi.nlm.nih.gov/2408087/	unknown, ADULT Health Status: unknown Age Group: ADULT Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/2408087/
Dilated pupils	Disc. AE	3.78 g single, oral Overdose Dose: 3.78 g Route: oral Route: single Dose: 3.78 g Sources: https://pubmed.ncbi.nlm.nih.gov/2408087/	unknown, ADULT Health Status: unknown Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/2408087/
Dizziness	Disc. AE	3.78 g single, oral Overdose Dose: 3.78 g Route: oral Route: single Dose: 3.78 g Sources: https://pubmed.ncbi.nlm.nih.gov/2408087/	unknown, ADULT Health Status: unknown Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/2408087/
Tachycardia	Disc. AE	4.9 g single, oral Overdose Dose: 4.9 g Route: oral Route: single Dose: 4.9 g Sources: https://pubmed.ncbi.nlm.nih.gov/2408087/	unknown, ADULT Health Status: unknown Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/2408087/
Dry mouth	9%	210 mg 1 times / day multiple, oral Recommended Dose: 210 mg, 1 times / day Route: oral Route: multiple Dose: 210 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/395129/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/395129/
Giddiness	9%	210 mg 1 times / day multiple, oral Recommended Dose: 210 mg, 1 times / day Route: oral Route: multiple Dose: 210 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/395129/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/395129/
Palpitation	6.5% Disc. AE	70 mg 3 times / day multiple, oral Recommended Dose: 70 mg, 3 times / day Route: oral Route: multiple Dose: 70 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/320827/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/320827/

PubMed

Title	Date	PubMed
Tricyclic antidepressants and headaches: systematic review and meta-analysis.	2010-10-20	20961988
Psychosocial issues in palliative care: a review of five cases.	2010-09	21218001
Trazodone effects on [H]-paroxetine and alpha(2)-adrenoreceptors in platelets of patients with major depression.	2010-05-25	20520789
Tryptophan, Neurodegeneration and HIV-Associated Neurocognitive Disorder.	2010	22084594
Drugs associated with more suicidal ideations are also associated with more suicide attempts.	2009-10-02	19798416
Effect of educational outreach on general practice prescribing of antibiotics and antidepressants: a two-year randomised controlled trial.	2009	19958063
Community-based randomised controlled trial evaluating falls and osteoporosis risk management strategies.	2008-11-04	18983670
Treating bipolar disorder in patients with renal failure having haemodialysis: two case reports.	2008-07-26	18655726
Folate augmentation of treatment - evaluation for depression (FolATED): protocol of a randomised controlled trial.	2007-11-15	18005429
Is untargeted educational outreach visiting delivered by pharmaceutical advisers effective in primary care? A pragmatic randomized controlled trial.	2007-07-26	17655748
Inflammatory multiple-sclerosis plaques generate characteristic metabolic profiles in cerebrospinal fluid.	2007-07-04	17611627
Neuropsychiatric manifestations of depression in multiple sclerosis: neuroinflammatory, neuroendocrine, and neurotrophic mechanisms in the pathogenesis of immune-mediated depression.	2007	17726912
Solid-phase extraction and analysis of 20 antidepressant drugs in human plasma by LC/MS with SSI method.	2006-10-16	16859851
Cost-effectiveness and cost-utility of tricyclic antidepressants, selective serotonin reuptake inhibitors and lofepramine: randomised controlled trial.	2006-04	16582060
A randomised controlled trial to compare the cost-effectiveness of tricyclic antidepressants, selective serotonin reuptake inhibitors and lofepramine.	2005-05	15876362
Enhancing central noradrenergic function in depression: is there still a place for a new antidepressant?	2005-03	18568121
Cutaneous adverse drug reaction to oral chlorphenamine detected with patch testing.	2005-01	15701135
Risk of fetal exposure to tricyclic antidepressants.	2004-10	15507199
The occurrence of selected human pharmaceutical compounds in UK estuaries.	2004-09	15325211
Current use of selective serotonin reuptake inhibitors and risk of acute myocardial infarction.	2004	15554748
Determination of selected human pharmaceutical compounds in effluent and surface water samples by high-performance liquid chromatography-electrospray tandem mass spectrometry.	2003-10-10	14570326
The promises and pitfalls of reboxetine.	2003	14647527
Managing MS. While a cure is sought, people with MS can help themselves.	2002-11	12523248
Treatment of multiple sclerosis with lofepramine, L-phenylalanine and vitamin B(12): mechanism of action and clinical importance: roles of the locus coeruleus and central noradrenergic systems.	2002-11	12376086
Nonpharmacological treatments for anxiety disorders.	2002-09	22034140
A randomised placebo controlled exploratory study of vitamin B-12, lofepramine, and L-phenylalanine (the "Cari Loder regime") in the treatment of multiple sclerosis.	2002-09	12185153
Simultaneous determination of seven tricyclic antidepressant drugs in human plasma by direct-injection HPLC-APCI-MS-MS with an ion trap detector.	2002-08	12142640
The effect of lofepramine and other related agents on the motility of Tetrahymena pyriformis.	2002-03-10	11869831
Antidepressants as risk factor for ischaemic heart disease: case-control study in primary care.	2001-09-22	11566831
MRI changes in multiple sclerosis following treatment with lofepramine and L-phenylalanine.	2001-07-03	11435905
Meta-analytical studies on new antidepressants.	2001	11719915
Comparison of the effects of antidepressants and their metabolites on reuptake of biogenic amines and on receptor binding.	1999-08	10379421
Pharmacological profile of antidepressants and related compounds at human monoamine transporters.	1997-12-11	9537821

Patents

Sample Use Guides

In Vivo Use Guide

The recommended dose for adults is one tablet to be taken 2 or 3 times a day

Route of Administration: Oral

In Vitro Use Guide

The mean value for the inhibition constant (Ki) for lofepramine in human parotid gland was 285 nM.

Substance Class	Chemical Created by `admin` on `Wed Apr 02 09:43:29 GMT 2025` Edited by `admin` on `Wed Apr 02 09:43:29 GMT 2025`
Record UNII	OCA4JT7PAW
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

LOFEPRAMINE [HSDB]

Preferred Name

English

LOFEPRAMINE

Official Name

English

Lofepramine [WHO-DD]

Common Name

English

LOFEPRAMINE [MI]

Common Name

English

4'-CHLORO-2-((3-(10,11-DIHYDRO-5H-DIBENZ(B,F)AZEPIN-5-YL)PROPYL)METHYLAMINO)ACETOPHENONE

Systematic Name

English

lofepramine [INN]

Common Name

English

LOFEPRAMINE [JAN]

Common Name

English

ETHANONE, 1-(4-CHLOROPHENYL)-2-((3-(10,11-DIHYDRO-5H-DIBENZ(B,F)AZEPIN-5-YL)PROPYL)METHYLAMINO)-

Systematic Name

English

Classification Tree Code System Code

WHO-VATC

QN06AA07