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

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 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
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
Managing MS. While a cure is sought, people with MS can help themselves.	2002 Nov	12523248
Nonpharmacological treatments for anxiety disorders.	2002 Sep	22034140
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
Solid-phase extraction and analysis of 20 antidepressant drugs in human plasma by LC/MS with SSI method.	2006 Oct 16	16859851
Drugs associated with more suicidal ideations are also associated with more suicide attempts.	2009 Oct 2	19798416
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.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 17:53:32 UTC 2023` Edited by `admin` on `Sat Dec 16 17:53:32 UTC 2023`
Record UNII	OCA4JT7PAW
Record Status	`Validated (UNII)`
Record Version

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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