Tesofensine

Tesofensine (also NS2330) is a synthetic triple monoamine reuptake inhibitor - it simultaneously inhibits the reuptake of dopamine, noradrenaline and serotonin in the brain. Originally tested for Alzheimer's and Parkinson's but disappointing there.

The exciting effects came unexpectedly: strong reduction in appetite and body fat. Phase 2 trials in obesity showed impressive results. After long legal issues around further development, tesofensine currently runs in Mexico under brand names as an anti-obesity drug.

Tesofensine elevates three neurotransmitters in the synaptic cleft:

• Dopamine: motivation, reward system - reduces "hedonic eating" (eating for pleasure).
• Noradrenaline: alertness, energy - raises basal metabolic rate and physical activity.
• Serotonin: satiety - reduces appetite via hypothalamus pathways.

This triple action is potent. Tesofensine shows significantly stronger fat-loss effects in studies than all currently approved oral anti-obesity drugs - with the exception of the GLP-1 class.

Oral capsule, once per day.

• 1 capsule with some water, in the morning.
• Morning is important: tesofensine is markedly stimulating and can disrupt sleep.
• On an empty stomach or with light food.

Tesofensine has compact but strong data in obesity research:

• Astrup et al. 2008: in a 6-month phase 2 study, patients on 0.5mg lost on average about 9% body weight - back then stronger than any other oral agent.
• Sjödin et al. 2010: combined with caloric restriction the effect was even more pronounced, plus improved insulin sensitivity.

Phase 3 was delayed by legal issues, now running again in Latin American markets.

• Elevated blood pressure and heart rate: via the noradrenaline effect. Caution with pre-existing hypertension.
• Sleep disturbance: common, especially in the first weeks and with evening dosing.
• Dry mouth: classic anticholinergic symptom.
• Irritability / mood swings: rare but more likely at higher doses.

Strict contraindication with MAO inhibitors, SSRIs, SNRIs and other serotonergic substances - serotonin syndrome risk. Also avoid methylene blue, tramadol, MDMA and similar.

Store dry, cool and protected from light, out of reach of children.