LOFEPRAMINE HYDROCHLORIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C26H27ClN2O.ClH
Molecular Weight	455.419
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.CN(CCCN1C2=C(CCC3=C1C=CC=C3)C=CC=C2)CC(=O)C4=CC=C(Cl)C=C4

InChI

InChIKey=ZWZIQPOLMDPIQM-UHFFFAOYSA-N

InChI=1S/C26H27ClN2O.ClH/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;1H

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
The effect of lofepramine and other related agents on the motility of Tetrahymena pyriformis.	2002 Mar 10	11869831
Nonpharmacological treatments for anxiety disorders.	2002 Sep	22034140
The promises and pitfalls of reboxetine.	2003 Winter	14647527
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
Tricyclic antidepressants and headaches: systematic review and meta-analysis.	2010 Oct 20	20961988

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 HYDROCHLORIDE

Official Name

English

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

Systematic Name

English

Lofepramine hydrochloride [WHO-DD]

Common Name

English

LOFEPRAMINE HYDROCHLORIDE [MART.]

Common Name

English

LOFEPRAMINE HYDROCHLORIDE [USAN]

Common Name

English

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

Common Name

English

LOFEPRAMINE HCL

Common Name

English

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

Systematic Name

English

AMPLIT

Brand Name

English

LOFEPRAMINE HYDROCHLORIDE [MI]

Common Name

English

WHR-2908A

Code

English

LOFEPRAMINE HYDROCHLORIDE [JAN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C265