TESOFENSINE TARTRATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C17H23Cl2NO.C4H6O6
Molecular Weight	478.363
Optical Activity	UNSPECIFIED
Defined Stereocenters	6 / 6
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O[C@H]([C@@H](O)C(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=RNHGKRXUMVFCTA-DRIRFIHHSA-N

InChI=1S/C17H23Cl2NO.C4H6O6/c1-3-21-10-14-13(9-12-5-7-17(14)20(12)2)11-4-6-15(18)16(19)8-11;5-1(3(7)8)2(6)4(9)10/h4,6,8,12-14,17H,3,5,7,9-10H2,1-2H3;1-2,5-6H,(H,7,8)(H,9,10)/t12-,13+,14+,17+;1-,2-/m01/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
Randomized trial of the triple monoamine reuptake inhibitor NS 2330 (tesofensine) in early Parkinson's disease.	2007 Feb 15	17149725
Gateways to clinical trials.	2007 Jan-Feb	17344945
Population pharmacokinetic modelling of NS2330 (tesofensine) and its major metabolite in patients with Alzheimer's disease.	2007 Jul	17324246
Contribution of the active metabolite M1 to the pharmacological activity of tesofensine in vivo: a pharmacokinetic-pharmacodynamic modelling approach.	2008 Jan	17982477
Weight loss produced by tesofensine in patients with Parkinson's or Alzheimer's disease.	2008 Jun	18356831
Tesofensine (NS 2330), a monoamine reuptake inhibitor, in patients with advanced Parkinson disease and motor fluctuations: the ADVANS Study.	2008 May	18474731
Gateways to clinical trials.	2008 Oct	19088949
Tesofensine--a novel potent weight loss medicine. Evaluation of: Astrup A, Breum L, Jensen TJ, Kroustrup JP, Larsen TM. Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial. Lancet 2008;372:1906-13.	2009 Jul	19548858
[The effect of tesofensine on body weight and body composition in obese subjects--secondary publication].	2009 Oct 5	19824222
Gateways to clinical trials.	2009 Sep	19907722
Semi-mechanistic population pharmacokinetic drug-drug interaction modelling of a long half-life substrate and itraconazole.	2010	20000889
Tackling obesity: new therapeutic agents for assisted weight loss.	2010 Apr 26	21437080
Quantitative pharmacology approach in Alzheimer's disease: efficacy modeling of early clinical data to predict clinical outcome of tesofensine.	2010 Jun	20077053

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 TARTRATE

Common Name

English

Code System Code Type Description

FDA UNII

3H98FB5747

Created by admin on Sat Dec 16 05:27:08 GMT 2023 , Edited by admin on Sat Dec 16 05:27:08 GMT 2023

PRIMARY

PUBCHEM

76966320

Created by admin on Sat Dec 16 05:27:08 GMT 2023 , Edited by admin on Sat Dec 16 05:27:08 GMT 2023

PRIMARY

DRUG BANK

DBSALT001992

Created by admin on Sat Dec 16 05:27:08 GMT 2023 , Edited by admin on Sat Dec 16 05:27:08 GMT 2023

PRIMARY

PARENT (SALT/SOLVATE)


					BLH9UKX9V1

TESOFENSINE

SUBSTANCE RECORD


					3H98FB5747

TESOFENSINE TARTRATE

AE	Significance	Dose	Population
Faeces hard	10.2%	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/
Abdominal pain	12.2%	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/
Dizziness	12.2%	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/
Vertigo2	16% Disc. AE	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/
Constipation	16.3%	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/
Insomnia	16.5%	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/
Diarrhoea	18.4%	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/
Dyssomnia	2%	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/
Ear and labyrinth disorders	2% Disc. AE	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/
Hypervigilance	2% Disc. AE	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/
Pain of skin	2% Disc. AE	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/
Vertigo	2% Disc. AE	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/
syncope	2% Disc. AE	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/
Nausea	22.4%	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/
Toothache	4.1%	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/
vomiting	4.1%	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/
Dry mouth	59.2%	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/
Faecaloma	6.1%	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/
Hypervigilance	6.1%	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/
Mood altered	8% Disc. AE	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/

Details

SMILES

InChI

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

Originator

Approval Year

Targets

Conditions

Approved Use

Approved Use

Approved Use

Doses

AEs

PubMed

Patents

Sample Use Guides

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