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
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
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 |
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 |
---|---|---|---|
Target ID: CHEMBL238 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24239329 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
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: |
unhealthy n = 49 Health Status: unhealthy Condition: obesity Sex: M+F Food Status: UNKNOWN Population Size: 49 Sources: |
Disc. AE: Mood altered, syncope... Other AEs: Nausea, vomiting... AEs leading to discontinuation/dose reduction: Mood altered (8%) Other AEs:syncope (2%) Vertigo (2%) Vertigo2 (16%) Pain of skin (2%) Hypervigilance (2%) Ear and labyrinth disorders (2%) Nausea (22.4%) Sources: 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%) |
AEs
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: |
unhealthy n = 49 Health Status: unhealthy Condition: obesity Sex: M+F Food Status: UNKNOWN Population Size: 49 Sources: |
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: |
unhealthy n = 49 Health Status: unhealthy Condition: obesity Sex: M+F Food Status: UNKNOWN Population Size: 49 Sources: |
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: |
unhealthy n = 49 Health Status: unhealthy Condition: obesity Sex: M+F Food Status: UNKNOWN Population Size: 49 Sources: |
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: |
unhealthy n = 49 Health Status: unhealthy Condition: obesity Sex: M+F Food Status: UNKNOWN Population Size: 49 Sources: |
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: |
unhealthy n = 49 Health Status: unhealthy Condition: obesity Sex: M+F Food Status: UNKNOWN Population Size: 49 Sources: |
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: |
unhealthy n = 49 Health Status: unhealthy Condition: obesity Sex: M+F Food Status: UNKNOWN Population Size: 49 Sources: |
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: |
unhealthy n = 49 Health Status: unhealthy Condition: obesity Sex: M+F Food Status: UNKNOWN Population Size: 49 Sources: |
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: |
unhealthy n = 49 Health Status: unhealthy Condition: obesity Sex: M+F Food Status: UNKNOWN Population Size: 49 Sources: |
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: |
unhealthy n = 49 Health Status: unhealthy Condition: obesity Sex: M+F Food Status: UNKNOWN Population Size: 49 Sources: |
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: |
unhealthy n = 49 Health Status: unhealthy Condition: obesity Sex: M+F Food Status: UNKNOWN Population Size: 49 Sources: |
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: |
unhealthy n = 49 Health Status: unhealthy Condition: obesity Sex: M+F Food Status: UNKNOWN Population Size: 49 Sources: |
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: |
unhealthy n = 49 Health Status: unhealthy Condition: obesity Sex: M+F Food Status: UNKNOWN Population Size: 49 Sources: |
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: |
unhealthy n = 49 Health Status: unhealthy Condition: obesity Sex: M+F Food Status: UNKNOWN Population Size: 49 Sources: |
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: |
unhealthy n = 49 Health Status: unhealthy Condition: obesity Sex: M+F Food Status: UNKNOWN Population Size: 49 Sources: |
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: |
unhealthy n = 49 Health Status: unhealthy Condition: obesity Sex: M+F Food Status: UNKNOWN Population Size: 49 Sources: |
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: |
unhealthy n = 49 Health Status: unhealthy Condition: obesity Sex: M+F Food Status: UNKNOWN Population Size: 49 Sources: |
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: |
unhealthy n = 49 Health Status: unhealthy Condition: obesity Sex: M+F Food Status: UNKNOWN Population Size: 49 Sources: |
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: |
unhealthy n = 49 Health Status: unhealthy Condition: obesity Sex: M+F Food Status: UNKNOWN Population Size: 49 Sources: |
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: |
unhealthy n = 49 Health Status: unhealthy Condition: obesity Sex: M+F Food Status: UNKNOWN Population Size: 49 Sources: |
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: |
unhealthy n = 49 Health Status: unhealthy Condition: obesity Sex: M+F Food Status: UNKNOWN Population Size: 49 Sources: |
PubMed
Title | Date | PubMed |
---|---|---|
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 |
|
Is new hope on the horizon for obesity? | 2008 Nov 29 |
|
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 |
|
Gateways to clinical trials. | 2009 Sep |
|
[Drug treatment of obesity--current situation and perspectives]. | 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 |
|
New approaches to the pharmacological treatment of obesity: can they break through the efficacy barrier? | 2010 Nov |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19548858
tesofensine 0.5 mg may cause almost double the weight loss
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/17982477
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
Edited
Fri Dec 15 15:54:03 GMT 2023
by
admin
on
Fri Dec 15 15:54:03 GMT 2023
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Record UNII |
1HJG8C744G
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Record Status |
Validated (UNII)
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Record Version |
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Created by
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