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
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
| 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 | C4H6O6 |
| Molecular Weight | 150.0868 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 2 / 2 |
| 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
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 |
|---|---|---|
| Chronic fluoxetine treatment induces brain region-specific upregulation of genes associated with BDNF-induced long-term potentiation. | 2007 |
|
| Triple reuptake inhibitors: the next generation of antidepressants. | 2008 Dec |
|
| Is new hope on the horizon for obesity? | 2008 Nov 29 |
|
| Gateways to clinical trials. | 2008 Oct |
|
| Triple reuptake inhibitors: a premise and promise. | 2008 Sep |
|
| 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 |
|
| [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
| Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 05:27:08 UTC 2023
by
admin
on
Sat Dec 16 05:27:08 UTC 2023
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| Record UNII |
3H98FB5747
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| Record Status |
Validated (UNII)
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| Record Version |
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3H98FB5747
Created by
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76966320
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DBSALT001992
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| Related Record | Type | Details | ||
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SOLVATE->ANHYDROUS | |||
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PARENT -> SALT/SOLVATE |
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