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
Chronic fluoxetine treatment induces brain region-specific upregulation of genes associated with BDNF-induced long-term potentiation.	2007	18301726
Tesofensine and weight loss.	2009 Feb 28	19249626
[Is there a future for medical treatment of obesity?].	2009 Oct 5	19814923
[Drug treatment of obesity--current situation and perspectives].	2010	21391349
The novel triple monoamine reuptake inhibitor tesofensine induces sustained weight loss and improves glycemic control in the diet-induced obese rat: comparison to sibutramine and rimonabant.	2010 Jun 25	20385125

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