TESOFENSINE CITRATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C17H23Cl2NO.C6H8O7
Molecular Weight	520.4
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)CC(O)(CC(O)=O)C(O)=O.CCOC[C@H]1[C@H]2CC[C@@H](C[C@@H]1C3=CC(Cl)=C(Cl)C=C3)N2C

InChI

InChIKey=ZIVJUFNVDKADJT-BEDQTAKTSA-N

InChI=1S/C17H23Cl2NO.C6H8O7/c1-3-21-10-14-13(9-12-5-7-17(14)20(12)2)11-4-6-15(18)16(19)8-11;7-3(8)1-6(13,5(11)12)2-4(9)10/h4,6,8,12-14,17H,3,5,7,9-10H2,1-2H3;13H,1-2H2,(H,7,8)(H,9,10)(H,11,12)/t12-,13+,14+,17+;/m0./s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/18474731 | https://www.ncbi.nlm.nih.gov/pubmed/11763162 | https://www.ncbi.nlm.nih.gov/pubmed/24239329

Tesofensine (also known as NS-2330) is a novel triple monoamine reuptake inhibitor with intrinsic inhibitory activity on norepinephrine (NE), serotonin (5-HT), and dopamine (DA) transporter function. It was development by NeuroSearch as a potential therapy for Alzheimer's disease (AD) and Parkinson's diseases, but these efforts have been discontinued. In phase II clinical trials with tesofensine in obese individuals, dose-related reductions in body weight, body fat and waist circumference, as well as improvements in other obesity-related endocrine factors were observed and the FDA recently endorsed the phase III trial program for this agent.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Dopamine transporter 180 Target ID: CHEMBL238 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24239329	Blocker 537

Conditions

Condition	Modality	Highest Phase	Product
Parkinson's disease 226 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17149725	Primary	Phase II 1132	Unknown Approved Use Unknown
Alzheimer’s disease 272 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11763162	Primary	Phase II 1132	Unknown Approved Use Unknown
Obesity 203 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19548858	Primary	Phase II 1132	Unknown Approved Use Unknown

Doses

Dose	Population	Adverse events
1 mg 1 times / day multiple, oral Highest studied dose Dose: 1 mg, 1 times / day Route: oral Route: multiple Dose: 1 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18950853/	unhealthy n = 49 Health Status: unhealthy Condition: obesity Sex: M+F Food Status: UNKNOWN Population Size: 49 Sources: https://pubmed.ncbi.nlm.nih.gov/18950853/	Disc. AE: Mood altered, syncope... Other AEs: Nausea, vomiting... AEs leading to discontinuation/dose reduction: Mood altered (8%) syncope (2%) Vertigo (2%) Vertigo2 (16%) Pain of skin (2%) Hypervigilance (2%) Ear and labyrinth disorders (2%) Other AEs: Nausea (22.4%) vomiting (4.1%) Dry mouth (59.2%) Toothache (4.1%) Abdominal pain (12.2%) Diarrhoea (18.4%) Constipation (16.3%) Faeces hard (10.2%) Faecaloma (6.1%) Insomnia (16.5%) Dyssomnia (2%) Hypervigilance (6.1%) Dizziness (12.2%) Sources: https://pubmed.ncbi.nlm.nih.gov/18950853/

AEs

PubMed

Title	Date	PubMed
Is new hope on the horizon for obesity?	2008 Nov 29	19041787
Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial.	2008 Nov 29	18950853
Gateways to clinical trials.	2008 Oct	19088949
Triple reuptake inhibitors: a premise and promise.	2008 Sep	20046357
Tesofensine and weight loss.	2009 Feb 28	19249626
Tesofensine and weight loss.	2009 Feb 28	19249625
Tesofensine, a monoamine reuptake inhibitor for the treatment of obesity.	2009 Oct	19777399
[The effect of tesofensine on body weight and body composition in obese subjects--secondary publication].	2009 Oct 5	19824222
[Is there a future for medical treatment of obesity?].	2009 Oct 5	19814923

Patents

Sample Use Guides

In Vivo Use Guide

tesofensine 0.5 mg may cause almost double the weight loss

Route of Administration: Oral

In Vitro Use Guide

In vitro investigations resulted in IC50 values for tesofensine of 11 and 1.7 nM for the [3 H]5-HT and [3 H]noradrenaline uptake, respectively.

Name

Type

Language

TESOFENSINE CITRATE

Common Name

English

TESOFENSINE CITRATE [MI]

Common Name

English

8-AZABICYCLO(3.2.1)OCTANE, 3-(3,4-DICHLOROPHENYL)-2-(ETHOXYMETHYL)-8-METHYL-, (1R,2R,3S,5S)-, 2-HYDROXY-1,2,3-PROPANETRICARBOXYLATE (1:1)

Systematic Name

English

Code System Code Type Description

CAS

861205-83-6