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

Molecular Formula	C17H23Cl2NO
Molecular Weight	328.277
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	4 / 4
E/Z Centers	0
Optical Activity	UNSPECIFIED

Molecular Formula	C6H8O7
Molecular Weight	192.1235
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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
Triple reuptake inhibitors: the next generation of antidepressants.	2008 Dec	19587855
Weight loss produced by tesofensine in patients with Parkinson's or Alzheimer's disease.	2008 Jun	18356831
Is new hope on the horizon for obesity?	2008 Nov 29	19041787
Gateways to clinical trials.	2008 Oct	19088949
A quantitative enterohepatic circulation model: development and evaluation with tesofensine and meloxicam.	2009	19705923
Polymorphisms of serotonin receptor 2A and 2C genes and COMT in relation to obesity and type 2 diabetes.	2009 Aug 19	19690620
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
Gateways to clinical trials.	2009 Sep	19907722
[Drug treatment of obesity--current situation and perspectives].	2010	21391349
Tackling obesity: new therapeutic agents for assisted weight loss.	2010 Apr 26	21437080
[Recent progress and novel perspectives on obesity pharmacotherapy].	2010 Aug	20857056
Subjective and objective effects of the novel triple reuptake inhibitor tesofensine in recreational stimulant users.	2010 Jul	20520602
Effect of centchroman coadministration on the pharmacokinetics of metformin in rats.	2010 Jun	20871764
Tesofensine, a novel triple monoamine reuptake inhibitor, induces appetite suppression by indirect stimulation of alpha1 adrenoceptor and dopamine D1 receptor pathways in the diet-induced obese rat.	2010 Jun	20200509
Quantitative pharmacology approach in Alzheimer's disease: efficacy modeling of early clinical data to predict clinical outcome of tesofensine.	2010 Jun	20077053
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
New approaches to the pharmacological treatment of obesity: can they break through the efficacy barrier?	2010 Nov	20688100
The effect of the triple monoamine reuptake inhibitor tesofensine on energy metabolism and appetite in overweight and moderately obese men.	2010 Nov	20479765

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.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 01:00:06 GMT 2023` Edited by `admin` on `Sat Dec 16 01:00:06 GMT 2023`
Record UNII	3R9T98ZB7U
Record Status	`Validated (UNII)`
Record Version

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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