LOFEPRAMINE

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=C(CCC3=C1C=CC=C3)C=CC=C2)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

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 8297	4.5 nM [IC50]
Serotonin transporter 178 Target ID: CHEMBL228 Sources: http://www.genome.jp/dbget-bin/www_bget?D08140 \| https://www.google.com/patents/US20120115149	Inhibitor 8297	7.15 null [pKi]
Norepinephrine transporter 191 Target ID: CHEMBL222 Sources: http://www.genome.jp/dbget-bin/www_bget?D08140 \| https://www.ncbi.nlm.nih.gov/pubmed/15076	Inhibitor 8297	8.27 null [pKi]
Muscarinic acetylcholine receptor 160 Target ID: CHEMBL2094109 Sources: https://www.ncbi.nlm.nih.gov/pubmed/3094050	Antagonist 2778	285.0 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Depression 235 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15876362 https://www.ncbi.nlm.nih.gov/pubmed/8794599	Primary		Approved 8429	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.

PubMed

Title	Date	PubMed
Pharmacological profile of antidepressants and related compounds at human monoamine transporters.	1997 Dec 11	9537821
Comparison of the effects of antidepressants and their metabolites on reuptake of biogenic amines and on receptor binding.	1999 Aug	10379421
Meta-analytical studies on new antidepressants.	2001	11719915
MRI changes in multiple sclerosis following treatment with lofepramine and L-phenylalanine.	2001 Jul 3	11435905
Antidepressants as risk factor for ischaemic heart disease: case-control study in primary care.	2001 Sep 22	11566831
Simultaneous determination of seven tricyclic antidepressant drugs in human plasma by direct-injection HPLC-APCI-MS-MS with an ion trap detector.	2002 Aug	12142640
The effect of lofepramine and other related agents on the motility of Tetrahymena pyriformis.	2002 Mar 10	11869831
Managing MS. While a cure is sought, people with MS can help themselves.	2002 Nov	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 Nov	12376086
Nonpharmacological treatments for anxiety disorders.	2002 Sep	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 Sep	12185153
Determination of selected human pharmaceutical compounds in effluent and surface water samples by high-performance liquid chromatography-electrospray tandem mass spectrometry.	2003 Oct 10	14570326
The promises and pitfalls of reboxetine.	2003 Winter	14647527
Current use of selective serotonin reuptake inhibitors and risk of acute myocardial infarction.	2004	15554748
Risk of fetal exposure to tricyclic antidepressants.	2004 Oct	15507199
The occurrence of selected human pharmaceutical compounds in UK estuaries.	2004 Sep	15325211
Cutaneous adverse drug reaction to oral chlorphenamine detected with patch testing.	2005 Jan	15701135
Enhancing central noradrenergic function in depression: is there still a place for a new antidepressant?	2005 Mar	18568121
A randomised controlled trial to compare the cost-effectiveness of tricyclic antidepressants, selective serotonin reuptake inhibitors and lofepramine.	2005 May	15876362
Cost-effectiveness and cost-utility of tricyclic antidepressants, selective serotonin reuptake inhibitors and lofepramine: randomised controlled trial.	2006 Apr	16582060
Solid-phase extraction and analysis of 20 antidepressant drugs in human plasma by LC/MS with SSI method.	2006 Oct 16	16859851
Neuropsychiatric manifestations of depression in multiple sclerosis: neuroinflammatory, neuroendocrine, and neurotrophic mechanisms in the pathogenesis of immune-mediated depression.	2007	17726912
Is untargeted educational outreach visiting delivered by pharmaceutical advisers effective in primary care? A pragmatic randomized controlled trial.	2007 Jul 26	17655748
Inflammatory multiple-sclerosis plaques generate characteristic metabolic profiles in cerebrospinal fluid.	2007 Jul 4	17611627
Folate augmentation of treatment - evaluation for depression (FolATED): protocol of a randomised controlled trial.	2007 Nov 15	18005429
Treating bipolar disorder in patients with renal failure having haemodialysis: two case reports.	2008 Jul 26	18655726
Community-based randomised controlled trial evaluating falls and osteoporosis risk management strategies.	2008 Nov 4	18983670
Effect of educational outreach on general practice prescribing of antibiotics and antidepressants: a two-year randomised controlled trial.	2009	19958063
Drugs associated with more suicidal ideations are also associated with more suicide attempts.	2009 Oct 2	19798416
Tryptophan, Neurodegeneration and HIV-Associated Neurocognitive Disorder.	2010	22084594
Trazodone effects on [H]-paroxetine and alpha(2)-adrenoreceptors in platelets of patients with major depression.	2010 May 25	20520789
Tricyclic antidepressants and headaches: systematic review and meta-analysis.	2010 Oct 20	20961988
Psychosocial issues in palliative care: a review of five cases.	2010 Sep	21218001

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.

Name

Type

Language

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 [HSDB]

Common 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