Tesofensine: Benefits and Risks

Tesofensine

Tesofensine (NS2330) is a serotonin–noradrenaline–dopamine reuptake inhibitor from the phenyltropane family of drugs, which is being developed for the treatment of obesity. R

 
 

Basics

 
800px-Tesofensine_chemical_structure.png
 

Tesofensine was originally used for the treatment of Alzheimer's and Parkinson's, but as of 2015 was dropped because trials showed limited efficacy for treatment. R R R R

Benefits

1. Helps with Weight Loss

 
 

Phase 2b trial (TIPO-1) results showed levels of weight loss over a 6-month period that were significantly greater than those achieved with any currently available drugs. R

2. Neuroprotective

 
 

Tesofensine also indirectly potentiates cholinergic neurotransmission. R

This has been proven to have beneficial effects on cognition, particularly in learning and memory. R

3. Anti-Depressant Effects

Sustained treatment with tesofensine has been shown to increase BDNF levels in the brain, and may possibly have an antidepressant effect. R

Potential Risks

Tesofensine has a long half life of about 9 days (220h). R

Tesofensine is metabolized by cytochorome P4503A4 (CYP3A4) to its desalkyl metabolite M1 NS2360. NS2360 is the only metabolite detectable in human plasma. R R

NS2360 has a longer half-life than tesofensine, approximately 16 days (374 h) in humans, and has an exposure of 31–34% of the parent compound at steady state.

In vivo data indicate that NS2360 is responsible for approximately 6% of the activity of tesofensine. As in animals, the kidney appears to play only a minor role in the clearance of tesofensine in humans (about 15–20%).

The most commonly reported side effects are dry mouth, headache, nausea, insomnia, diarrhea and constipation. Some have reported blood pressure and heart rate increase. R R R

More Research

  • Tesofensine has IC50 of 8.0, 3.2 and 11.0nM at the DAT, NAT and 5HTT. R
  • New data showed IC50 (nM) NE 1.7, SER 11, DA 65. R R

So I'm not sure which is right.