U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C17H23Cl2NO.C4H6O6.H2O
Molecular Weight 496.379
Optical Activity UNSPECIFIED
Defined Stereocenters 6 / 6
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TESOFENSINE TARTRATE MONOHYDRATE

SMILES

O.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=MLBOTABDHOAIGP-ZUVYWPKOSA-N
InChI=1S/C17H23Cl2NO.C4H6O6.H2O/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);1H2/t12-,13+,14+,17+;1-,2-;/m01./s1

HIDE SMILES / InChI
Molecular Formula H2O
Molecular Weight 18.0153
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE
Molecular Formula C4H6O6
Molecular Weight 150.0868
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED
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

Description

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

Unknown
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
Blocker
537
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Doses

Doses

DosePopulationAdverse 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

AEs

AESignificanceDosePopulation
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/
PubMed

PubMed

TitleDatePubMed
Chronic fluoxetine treatment induces brain region-specific upregulation of genes associated with BDNF-induced long-term potentiation.
2007
Randomized trial of the triple monoamine reuptake inhibitor NS 2330 (tesofensine) in early Parkinson's disease.
2007 Feb 15
Expression of brain derived neurotrophic factor, activity-regulated cytoskeleton protein mRNA, and enhancement of adult hippocampal neurogenesis in rats after sub-chronic and chronic treatment with the triple monoamine re-uptake inhibitor tesofensine.
2007 Jan 26
Gateways to clinical trials.
2007 Jan-Feb
Population pharmacokinetic modelling of NS2330 (tesofensine) and its major metabolite in patients with Alzheimer's disease.
2007 Jul
Triple reuptake inhibitors: the next generation of antidepressants.
2008 Dec
Contribution of the active metabolite M1 to the pharmacological activity of tesofensine in vivo: a pharmacokinetic-pharmacodynamic modelling approach.
2008 Jan
Weight loss produced by tesofensine in patients with Parkinson's or Alzheimer's disease.
2008 Jun
Tesofensine (NS 2330), a monoamine reuptake inhibitor, in patients with advanced Parkinson disease and motor fluctuations: the ADVANS Study.
2008 May
Is new hope on the horizon for obesity?
2008 Nov 29
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
Gateways to clinical trials.
2008 Oct
Triple reuptake inhibitors: a premise and promise.
2008 Sep
A quantitative enterohepatic circulation model: development and evaluation with tesofensine and meloxicam.
2009
Polymorphisms of serotonin receptor 2A and 2C genes and COMT in relation to obesity and type 2 diabetes.
2009 Aug 19
Tesofensine and weight loss.
2009 Feb 28
Tesofensine and weight loss.
2009 Feb 28
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
Tesofensine, a monoamine reuptake inhibitor for the treatment of obesity.
2009 Oct
[The effect of tesofensine on body weight and body composition in obese subjects--secondary publication].
2009 Oct 5
[Is there a future for medical treatment of obesity?].
2009 Oct 5
Gateways to clinical trials.
2009 Sep
[Drug treatment of obesity--current situation and perspectives].
2010
Semi-mechanistic population pharmacokinetic drug-drug interaction modelling of a long half-life substrate and itraconazole.
2010
Tackling obesity: new therapeutic agents for assisted weight loss.
2010 Apr 26
[Recent progress and novel perspectives on obesity pharmacotherapy].
2010 Aug
Subjective and objective effects of the novel triple reuptake inhibitor tesofensine in recreational stimulant users.
2010 Jul
Effect of centchroman coadministration on the pharmacokinetics of metformin in rats.
2010 Jun
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
Quantitative pharmacology approach in Alzheimer's disease: efficacy modeling of early clinical data to predict clinical outcome of tesofensine.
2010 Jun
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
Pharmacological management of appetite expression in obesity.
2010 May
New approaches to the pharmacological treatment of obesity: can they break through the efficacy barrier?
2010 Nov
The effect of the triple monoamine reuptake inhibitor tesofensine on energy metabolism and appetite in overweight and moderately obese men.
2010 Nov
Patents

Patents

06288079
4
06395748
6
JP2011529923A
42

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 Fri Dec 15 15:54:03 UTC 2023
Edited
by admin
on Fri Dec 15 15:54:03 UTC 2023
Record UNII
1HJG8C744G
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TESOFENSINE TARTRATE MONOHYDRATE
Common Name English
NS-2330 TARTRATE MONOHYDRATE
Common Name English
Code System Code Type Description
FDA UNII
1HJG8C744G
Created by admin on Fri Dec 15 15:54:03 UTC 2023 , Edited by admin on Fri Dec 15 15:54:03 UTC 2023
PRIMARY
PUBCHEM
76964625
Created by admin on Fri Dec 15 15:54:03 UTC 2023 , Edited by admin on Fri Dec 15 15:54:03 UTC 2023
PRIMARY
Related Record Type Details
Structure of TESOFENSINE TARTRATE
ANHYDROUS->SOLVATE
Structure of TESOFENSINE
PARENT -> SALT/SOLVATE
Structure of TARTARIC ACID
PARENT -> SALT/SOLVATE
Related Record Type Details
Structure of TESOFENSINE
ACTIVE MOIETY
NIH
NCATS
PRIVACY ACT
ACCESSIBILITY
DISCLAIMER
HHS VULNERABILITY DISCLOSURE
For language access assistance, contact the NCATS Public Information Officer
National Center for Advancing Translational Sciences (NCATS),
6701 Democracy Boulevard, Bethesda MD 20892-4874 • 301-594-8966