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

Details

Stereochemistry ABSOLUTE
Molecular Formula C17H23Cl2NO
Molecular Weight 328.277
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TESOFENSINE

SMILES

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

InChI

InChIKey=VCVWXKKWDOJNIT-ZOMKSWQUSA-N
InChI=1S/C17H23Cl2NO/c1-3-21-10-14-13(9-12-5-7-17(14)20(12)2)11-4-6-15(18)16(19)8-11/h4,6,8,12-14,17H,3,5,7,9-10H2,1-2H3/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

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
Contribution of the active metabolite M1 to the pharmacological activity of tesofensine in vivo: a pharmacokinetic-pharmacodynamic modelling approach.
2008 Jan
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
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
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
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
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 Sat Dec 16 16:57:46 GMT 2023
Edited
by admin
on Sat Dec 16 16:57:46 GMT 2023
Record UNII
BLH9UKX9V1
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TESOFENSINE
INN   MART.   MI   WHO-DD  
INN  
Official Name English
NS2330
Code English
TESOFENSINE [MI]
Common Name English
tesofensine [INN]
Common Name English
Tesofensine [WHO-DD]
Common Name English
NS-2330
Code English
TESOFENSINE [MART.]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C265
Created by admin on Sat Dec 16 16:57:47 GMT 2023 , Edited by admin on Sat Dec 16 16:57:47 GMT 2023
FDA ORPHAN DRUG 804220
Created by admin on Sat Dec 16 16:57:47 GMT 2023 , Edited by admin on Sat Dec 16 16:57:47 GMT 2023
FDA ORPHAN DRUG 804320
Created by admin on Sat Dec 16 16:57:47 GMT 2023 , Edited by admin on Sat Dec 16 16:57:47 GMT 2023
Code System Code Type Description
WIKIPEDIA
Tesofensine
Created by admin on Sat Dec 16 16:57:47 GMT 2023 , Edited by admin on Sat Dec 16 16:57:47 GMT 2023
PRIMARY
ChEMBL
CHEMBL2107788
Created by admin on Sat Dec 16 16:57:47 GMT 2023 , Edited by admin on Sat Dec 16 16:57:47 GMT 2023
PRIMARY
EVMPD
SUB20754
Created by admin on Sat Dec 16 16:57:47 GMT 2023 , Edited by admin on Sat Dec 16 16:57:47 GMT 2023
PRIMARY
EPA CompTox
DTXSID70905114
Created by admin on Sat Dec 16 16:57:47 GMT 2023 , Edited by admin on Sat Dec 16 16:57:47 GMT 2023
PRIMARY
DRUG BANK
DB06156
Created by admin on Sat Dec 16 16:57:47 GMT 2023 , Edited by admin on Sat Dec 16 16:57:47 GMT 2023
PRIMARY
MESH
C518479
Created by admin on Sat Dec 16 16:57:47 GMT 2023 , Edited by admin on Sat Dec 16 16:57:47 GMT 2023
PRIMARY
MERCK INDEX
m10592
Created by admin on Sat Dec 16 16:57:47 GMT 2023 , Edited by admin on Sat Dec 16 16:57:47 GMT 2023
PRIMARY Merck Index
INN
8343
Created by admin on Sat Dec 16 16:57:47 GMT 2023 , Edited by admin on Sat Dec 16 16:57:47 GMT 2023
PRIMARY
PUBCHEM
11370864
Created by admin on Sat Dec 16 16:57:47 GMT 2023 , Edited by admin on Sat Dec 16 16:57:47 GMT 2023
PRIMARY
FDA UNII
BLH9UKX9V1
Created by admin on Sat Dec 16 16:57:47 GMT 2023 , Edited by admin on Sat Dec 16 16:57:47 GMT 2023
PRIMARY
CAS
195875-84-4
Created by admin on Sat Dec 16 16:57:47 GMT 2023 , Edited by admin on Sat Dec 16 16:57:47 GMT 2023
PRIMARY
NCI_THESAURUS
C66589
Created by admin on Sat Dec 16 16:57:47 GMT 2023 , Edited by admin on Sat Dec 16 16:57:47 GMT 2023
PRIMARY
SMS_ID
100000086513
Created by admin on Sat Dec 16 16:57:47 GMT 2023 , Edited by admin on Sat Dec 16 16:57:47 GMT 2023
PRIMARY
Related Record Type Details
Structure of TESOFENSINE TARTRATE
SALT/SOLVATE -> PARENT
Structure of TESOFENSINE CITRATE
SALT/SOLVATE -> PARENT
Structure of TESOFENSINE TARTRATE MONOHYDRATE
SALT/SOLVATE -> PARENT
Related Record Type Details
Structure of TESOFENSINE
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