| Identification | Back Directory | [Name]
tesofensine | [CAS]
195875-84-4 | [Synonyms]
Tesofensine-13C-d3
(1S,3S,4R,5R)-3-(3,4-dichlorophenyl)-4-(ethoxymethyl)-8-methyl-8-azabicyclo[3.2.1]octane
(1R,2R,3S,5S)-3-(3,4-Dichlorophenyl)-2-(ethoxymethyl)-8-methyl-8-azabicyclo[3.2.1]octane
8-Azabicyclo[3.2.1]octane, 3-(3,4-dichlorophenyl)-2-(ethoxymethyl)-8-methyl-, (1R,2R,3S,5S)- | [Molecular Formula]
C17H23Cl2NO | [MDL Number]
MFCD25976398 | [MOL File]
195875-84-4.mol | [Molecular Weight]
328.28 |
| Chemical Properties | Back Directory | [Boiling point ]
396.6±42.0 °C(Predicted) | [density ]
1.161±0.06 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMF: 2 mg/mL,DMSO: 1 mg/mL,Ethanol: Slightly soluble,PBS (pH 7.2): 0.14 mg/mL | [form ]
A solid | [pka]
10.46±0.60(Predicted) | [color ]
White to off-white | [Stability:]
Hygroscopic | [InChI]
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 | [InChIKey]
VCVWXKKWDOJNIT-ZOMKSWQUSA-N | [SMILES]
[C@@]12([H])N(C)[C@@]([H])(CC1)C[C@H](C1=CC=C(Cl)C(Cl)=C1)[C@H]2COCC |
| Hazard Information | Back Directory | [Description]
Tesofensine ((1R, 2R, 3S, 5S)-3-(3, 4-dichlorophenyl)-2-(ethoxymethyl)-8-methyl-8-azabicyclo[3.2.1]octane)) is an inhibitor of neuronal reuptake of dopamine, noradrenaline, and serotonin. Tesofensine was developed for the treatment of Alzheimer's and Parkinson's disease but lacked efficacy. Meta-analysis revealed that tesofensine (0.125–1.0 mg, once daily; oral) produced dose-dependent weight loss, and 32% of obese patients had ≥ 5% weight loss following 14 wk of treatment. Weight loss was accompanied by hypophagia, suggesting an appetite suppressant action[2].
| [History]
Tesofensine is a dopamine, serotonin, and noradrenaline (triple) reuptake inhibitor originally developed by NeuroSearch for the treatment of Alzheimer's disease and Parkinson's disease. Development of the compound for these neurological indications was unsuccessful but significant weight loss was reported during the clinical trials in Parkinson's disease. Hence, tesofensine is now being developed by NeuroSearch for the treatment of obesity and type 2 diabetes[1].
| [Uses]
Tesofensine, is a serotonin–noradrenaline–dopamine reuptake inhibitor from the phenyltropane family of drugs, which is currently in clinical development for the treatment of obesity. | [in vivo]
Tesofensine (a single dose of 0.1-3? mg/kg, s.c.) induces hypophagia in the DIO rat. A single dose of Tesofensine (0. 1-3?mg/kg, s.c.) robustly and dose dependently inhibits food intake in DIO rats over the 12?h nocturnal observation period. Daily administration of a moderate dose of Tesofensine (2.0?mg/kg, s.c.) over 16 days triggers a significant reduction in body weight after 4 days of administration relative to vehicle-treated controls[3]. | Animal Model: | Diet-induced obesity (DIO) rat[3] | | Dosage: | 0.1-3?mg/kg | | Administration: | Administered subcutaneously (s.c.); a single dose (acute treatment) | | Result: | The threshold dose for inhibition of total food intake was 1.0?mg/kg.
The ED50 for inhibition of total food intake in DIO rats was estimated to be 1.3?mg/kg.
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| Animal Model: | Diet-induced obesity (DIO) rat[3] | | Dosage: | 2.0?mg/kg | | Administration: | Administered subcutaneously (s.c.) daily for over 16 days (chronic treatment) | | Result: | The average relative decrease in the body weight of tesofensine-treated DIO rats over the entire treatment period was 8.6±1.4%.
When comparing to vehicle controls, the relative weight loss with tesofensine was 13.8±1.4%.
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| [storage]
Store at -20°C | [References]
[1] Dourish, C. J. Wilding and J. Halford. “Anti-obesity Drugs: From Animal Models to Clinical Efficacy.”Animal and Translational Models for CNS Drug Discovery 2008: 271-315.
[2] Vidya Narayanaswami, Linda P. Dwoskin. “Obesity: Current and potential pharmacotherapeutics and targets.” Pharmacology Therapeutics 170 (2017): Pages 116-147.
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