Tesofensine is a pharmaceutical compound originally explored for treating neurological conditions like Parkinson’s and Alzheimer’s disease. During these initial studies, researchers consistently observed weight loss as a side effect, particularly in individuals who were overweight. This finding prompted a shift in its development towards becoming a potential treatment for obesity.
How Tesofensine Influences Brain Chemistry
Tesofensine functions as a triple reuptake inhibitor, blocking the reabsorption of serotonin, noradrenaline (also known as norepinephrine), and dopamine. This action increases the concentration of these chemical messengers in the spaces between nerve cells, enhancing their availability to transmit signals.
Serotonin is widely associated with mood, appetite, and sleep regulation. Noradrenaline is involved in the body’s fight-or-flight response, affecting alertness, arousal, and attention. Dopamine is central to the brain’s reward and motivation systems, influencing pleasure, focus, and movement.
Impact on Weight Management
The changes in brain chemistry lead to its effects on weight management. The increased availability of serotonin and other neurotransmitters in brain regions that control appetite results in a reduction in hunger. Clinical trial participants often report feeling full sooner and for longer periods after eating, a sensation known as increased satiety.
Tesofensine also reduces cravings for highly palatable, calorie-dense foods. By modulating the dopamine-driven reward pathways, the drug can diminish the desire for sugary or fatty foods. This effect, combined with appetite suppression, contributes to substantial weight loss. The reduction in body weight is primarily due to a loss of fat mass, as evidenced by decreases in waist circumference.
A phase IIb trial showed that participants taking tesofensine experienced more weight loss than those taking a placebo. Over a 24-week period, patients on a 0.5 mg dose lost an average of 9.2% of their body weight, compared to a 2.2% loss in the placebo group. In a longer-term extension study, individuals treated with 0.5 mg of tesofensine for 48 weeks achieved an average total weight loss of 13 to 14 kg.
Effects on Cognitive Function and Mood
Beyond its impact on weight, tesofensine has demonstrated potential effects on cognition and mood. The elevation of serotonin and noradrenaline levels may produce an antidepressant-like effect, leading to improvements in overall mood. Some studies have suggested that the drug could have added benefits for individuals with obesity who also experience symptoms of depression or anxiety.
The increase in dopamine and noradrenaline may also lead to enhanced cognitive functions. These changes can affect executive functions, which include processes like planning, focus, and organizing tasks. Early research has suggested that sustained treatment with tesofensine could increase levels of brain-derived neurotrophic factor (BDNF), a protein involved in nerve cell survival and growth, which may point toward neuroprotective qualities. However, some studies have noted that higher doses might be associated with feelings of confusion or agitation.
Safety Profile and Regulatory Status
Several common side effects have been identified for tesofensine. The most frequently reported adverse events include dry mouth, insomnia, constipation, nausea, and headache. A dose-dependent increase in heart rate of up to 8 beats per minute and minor increases in blood pressure of 1-3 mmHg have also been observed, particularly at therapeutically relevant doses.
Despite showing promising results in weight loss trials, tesofensine has not obtained approval from the U.S. Food and Drug Administration (FDA). Its original developer, NeuroSearch, transferred the rights to another company, and its development for Alzheimer’s and Parkinson’s disease was discontinued. It is not a commercially available prescription medication for weight loss in most parts of the world.