Tesofensine (NS2330) is a triple monoamine reuptake inhibitor that blocks the reuptake of dopamine, norepinephrine, and serotonin.
Last reviewed: 2026-08-18
Also known as
Status: Investigational - not FDA approved for obesity treatment in the US
Full composition (formula, molecular weight, sequence) in Quick Facts →
A 6-month randomized, double-blind, placebo-controlled phase 2 trial (Astrup et al., Lancet 2008) reported dose-dependent weight loss of up to ~10% of body weight with tesofensine 0.5 mg/day. That publication carries a 2013 Expression of Concern from The Lancet over trial irregularities. Phase 3 development stalled when the original sponsor ran into difficulties, and the drug is not approved anywhere.
Animal studies show tesofensine reduces food intake and increases energy expenditure/thermogenesis, consistent with triple monoamine reuptake inhibition.
Cell-based assays confirm potent inhibition of dopamine, norepinephrine, and serotonin transporters.
Cardiovascular signals (heart-rate and blood-pressure increases) and the reliability of the pivotal weight-loss data are major open questions; off-label/gray-market use is unregulated.
A phase 2 RCT reported dose-dependent weight loss (up to ~10% body weight at 0.5 mg/day over 24 weeks) in obese patients; the paper later received an Expression of Concern over trial irregularities.
The Lancet issued an Expression of Concern about the 2008 tesofensine trial due to irregularities in trial conduct.
No side effects data available yet.
This peptide may have limited safety data.
Reported values from research literature and community protocols. Educational reference only — not a dosing recommendation or medical advice.
0.5mg
Research protocols are for educational purposes only. Always consult qualified medical professionals.
No. It is not approved anywhere; phase 3 development stalled and the main phase 2 paper carries a Lancet Expression of Concern.
The 2008 phase 2 trial reported up to ~10% body-weight loss at 0.5 mg/day over 24 weeks, but the reliability of those data is disputed.
As NS2330 it was tested for Parkinson's and Alzheimer's disease before its weight-loss effect redirected development toward obesity.
TIPO-1 Phase IIB Trial (2008)
(2008)
TIPO-4 Extension Trial (48 weeks)
()
Viking Phase 3 Trial (2018)
(2018)
Mechanism
Tesofensine is a triple monoamine reuptake inhibitor that blocks reuptake of dopamine (IC50: 6.5nM), norepinephrine (IC50: 1.7nM), and serotonin (IC50: 11nM). This increases neurotransmitter levels in the hypothalamus and other brain regions controlling appetite and satiety. Recent research shows it silences GABAergic neurons in the lateral hypothalamus that normally promote feeding behavior.
NOT FDA approved - investigational compound only. May increase heart rate by 5-8 bpm (dose-dependent). Can modestly increase blood pressure (1-3 mmHg typical). Contraindicated with MAOIs, SSRIs, SNRIs, and stimulants. Not recommended for those with cardiovascular disease or uncontrolled hypertension. May cause insomnia - take in the morning only. Psychiatric effects possible - avoid with depression/anxiety history. Long half-life means side effects persist if they occur. Regular cardiovascular monitoring recommended.
1.TIPO-1 Phase IIB Trial (2008)
(2008)
2.TIPO-4 Extension Trial (48 weeks)
()
3.Viking Phase 3 Trial (2018)
(2018)