Tesofensine is a drug originally developed to treat Alzheimer's and Parkinson's disease but was found to cause significant weight loss in trial participants. Tesofensine works by blocking the reabsorption of three neurotransmitters in the brain - serotonin, noradrenaline, and dopamine - which increases their levels and makes more of them available to use. Blocking dopamine re-uptake reduces cravings and desire for specific foods, while increasing serotonin reduces physical hunger needs and associated symptoms like stomach growling. Noradrenaline increases the basal metabolic rate, which can contribute to weight loss.
A 2008 clinical trial showed that those who took tesofensine lost more weight than those who took a placebo, with those taking the highest doses losing the most weight. Tesofensine also had a positive effect on appetite measures, such as reducing hunger and the desire for unhealthy foods. The medication also improved quality of life, including physical function and self-esteem. In a 14-day trial, tesofensine still resulted in more weight loss than a placebo, even without a calorie-restricted diet or exercise program. Weight loss was also sustained in longer trials. Tesofensine may also increase brain-derived neurotrophic factor (BDNF) production, which can improve brain function and potentially aid in weight loss.
However, Tesofensine has side effects, and higher doses of the drug increase their frequency and severity. One of these is an increase in blood pressure, which can lead to a range of cardiovascular issues. Other side effects include: