Tesofensine/cas 402856-42-2

Tesofensine primarily acts as an appetite suppressant but possibly also acts by increasing resting energy expenditure. A recent study showed that tesofensine modulates neuronal activity of the lateral hypothalamus, silencing GABAergic neurons, a brain region involved in feeding.
Phase II clinical trials for the treatment of obesity have been successfully completed. Phase IIB trial (TIPO-1) results reported in The Lancet showed levels of weight loss over a 6-month period that were significantly greater than those achieved with any currently available drugs. Patients lost an average of 12.8 kg on the 1 mg dose, 11.3 kg on the 0.5 mg dose, and 6.7 kg on the 0.25 mg dose, compared with a 2.2 kg loss in the placebo group.
In general, the safety profile of tesofensine is similar to currently approved medications for the treatment of obesity. The most commonly reported side effects in the obese population were dry mouth, headache, nausea, insomnia, diarrhea, and constipation. A dose-dependent pattern was observed for dry mouth and insomnia. The overall withdrawal rate due to adverse events in clinical trials in the obese population was 13% with tesofensine and 6% with placebo. Blood pressure and heart rate increases with the therapeutically relevant doses of tesofensine (0.25 mg and 0.5 mg) were 1–3 mmHg and up to 8 bpm, respectively. 
Tesofensine also indirectly potentiates cholinergic neurotransmission, proven to have beneficial effects on cognition, particularly in learning and memory. Sustained treatment with tesofensine has been shown to increase BDNF levels in the brain and may possibly have an antidepressant effect.