Tesofensine

Tesofensine is an oral compound studied for weight loss — it works by affecting three brain chemicals (serotonin, norepinephrine, and dopamine) that influence appetite, and it's grouped in this library alongside peptide fat-loss compounds even though it's a small molecule, not a peptide. It was originally developed for Alzheimer's and Parkinson's and repurposed after weight loss turned up as a side effect. It remains investigational and is not FDA-approved.

Tesofensine has been studied for weight loss. In a Phase 2b trial (TIPO-1), it was associated with dose-dependent weight loss over 24 weeks. It has a very long half-life (about 9 days for the parent compound), so its levels build over weeks and persist after stopping. Reported side effects include dry mouth, insomnia, and small increases in blood pressure and heart rate.

Not FDA-approved. Investigational New Drug. Originally developed by NeuroSearch (Denmark) for Alzheimer's and Parkinson's (dropped for lack of efficacy), then repurposed for obesity after consistent weight-loss as an adverse event. Rights transferred to Saniona (2014). Phase 2 (TIPO-1) completed; a Phase 3 obesity registration trial (the Medix "VIKING" study in Mexico, n=372, 24 weeks, 0.25 and) was announced on 17 December 2018 as having met its primary and secondary endpoints. No FDA approval as of last review. Mexico is the compound's furthest-advanced regulatory position: Saniona's partner Medix filed a new-drug application with the Mexican regulator COFEPRIS, whose technical committee issued a favorable opinion in February 2023 — but per the sponsor's own pipeline and investor communications the application had not received final approval, and tesofensine should not be described as "approved in Mexico". Not DEA-scheduled (but is a triple monoamine reuptake inhibitor — abuse-liability profile was specifically studied, see below). Oral. WADA-banned (in-competition) — tesofensine is explicitly named in the WADA 2026 Prohibited List under S6 (Stimulants). ✓ verified 2026-05-30 against the archived 2026 list. ⚠️ Note: S6 stimulants are prohibited in-competition only (unlike the S2/S4 substances prohibited at all times) — the distinction matters for competing athletes.

Tesofensine is investigational, not FDA-approved, and is taken orally — there is nothing to reconstitute. It is named on the WADA Prohibited List under stimulants (S6), prohibited in-competition. Combining it with other serotonergic drugs raises serotonin-syndrome risk. VialWise is a research and educational reference, not medical advice — consult a licensed professional.

⚠️ For research and educational purposes only. Tesofensine is an unapproved investigational drug. Information in this entry is informational, not medical advice. Always consult appropriate professional guidance before any decisions.

⚠️ Tesofensine is not a peptide and not injectable. It is a small-molecule oral triple monoamine reuptake inhibitor (serotonin + norepinephrine + dopamine). The Vialwise reconstitution calculator does not apply — there is nothing to reconstitute. It is included in the library only because it is frequently asked about alongside peptide fat-loss compounds; mechanistically it has nothing in common with them.

⚠️ Very long half-life (~9–10 days) — effects and side effects accumulate. Tesofensine's ~234-hour half-life means steady-state plasma levels build over weeks and persist long after stopping. Its active metabolite (NS2360) has an even longer half-life (~16 days). This is unusual and matters: dose changes take a long time to fully manifest, and the compound lingers after discontinuation. CYP3A4-metabolized → drug-interaction potential.

Tesofensine (NS2330) is a small-molecule oral appetite suppressant in the triple-monoamine-reuptake-inhibitor class, investigational for obesity. It is not a peptide — its inclusion here is purely because the research-supply community asks about it alongside peptide fat-loss compounds.

Mechanism. Tesofensine inhibits the reuptake of norepinephrine, serotonin, and dopamine — predominantly noradrenergic and serotonergic, with weaker dopaminergic activity. (Commonly quoted IC50 values of NET 1.7 nM, SERT 11 nM and DAT 65 nM are — they are not tied to a confirmed primary source in this entry, though the NET > SERT > DAT rank order is well established.) A 2025 cryo-EM study resolved the dopamine transporter bound to tesofensine and several other triple-reuptake inhibitors, showing it stabilizes DAT in an outward-facing conformation.[⁵] The dominant clinical effect is appetite suppression; preclinical work suggests it also modulates lateral-hypothalamic GABAergic neurons involved in feeding, and may raise resting energy expenditure. The relatively weak DAT inhibition is thought to explain both its limited Parkinson's efficacy and its low self-administration / abuse liability in stimulant-user studies.

Development history. Originally developed by NeuroSearch for Alzheimer's and Parkinson's disease; dropped for those after early trials showed limited efficacy. Weight loss was a consistent adverse event in those studies, prompting repurposing for obesity. The Phase 2b TIPO-1 trial (Astrup et al., Lancet 2008) showed substantial weight loss; an open-label extension (TIPO-4) and a later Phase 3 registration trial followed — the Medix-run "VIKING" study in Mexico (n=372, 24 weeks, double-blind, placebo-controlled, 0.25 and), announced 17 December 2018 as having met its primary and secondary endpoints. Rights moved from NeuroSearch to Saniona in 2014. Still not FDA-approved.

Efficacy (TIPO-1, Phase 2b, 24 weeks).[¹] On a 300-kcal-deficit diet, mean weight loss was −6.7 kg, −11.3 kg, −12.8 kg vs −2.2 kg placebo. Placebo-subtracted: 4.5% / 9.2% / 10.6% by dose — roughly double the FDA-approved obesity drugs available in 2008. These are the numbers driving community interest.

Regulatory status. Investigational; not FDA-approved, not DEA-scheduled. Oral.

Mexico — the furthest-advanced regulatory position, and a common source of misinformation. Saniona's partner Medix submitted a new-drug application for tesofensine in obesity to Mexico's regulator, COFEPRIS, whose technical committee issued a favorable opinion in February 2023. Per the sponsor's own pipeline page and investor releases, the application had not received final approval as of the most recent communications. ⚠️ Vendor and blog sources claiming tesofensine is "approved in Mexico as Tesomet or Nupenta since 2023" are not supported by the sponsor's filings, and they appear to conflate two different products — Tesomet is a separate Saniona combination product (tesofensine plus metoprolol) developed for rare disease indications such as Prader-Willi and hypothalamic obesity, not the plain-tesofensine obesity registration. Treat any "approved in Mexico" claim as unverified.

⚠️ WADA-banned (in-competition): tesofensine is explicitly named in the WADA 2026 Prohibited List under S6 (Stimulants) — verified against the locally-archived 2026 list (`docs/legal/wada-2026-prohibited-list.txt`, S6 stimulants section + index), and independently corroborated by a 2026 peer-reviewed anti-doping paper which states it is classified under S6 stimulants and prohibited in-competition only.[⁴] S6 stimulants are prohibited in-competition only (unlike the S2/S4 substances prohibited at all times), so the distinction matters for competing athletes. That same paper reported urinary detection windows of up to 500 hours after a dose, with four principal metabolites and marked interindividual variability.[⁴] Confirm against the most recent annual edition before competition.

Commonly reported

• Dry mouth (dose-dependent)
• Insomnia (dose-dependent)
• Headache, nausea, diarrhea, constipation
• Blood pressure increase (1–3 mmHg) and heart rate increase (up to ~8 bpm) at therapeutic doses
• Trial withdrawal due to adverse events: ~13% tesofensine vs ~6% placebo

Serious

• Signs of serotonin syndrome (agitation, hyperthermia, clonus, autonomic instability) — especially if combined with serotonergic drugs
• Significant blood-pressure or heart-rate elevation, palpitations, chest pain
• Mood changes / psychiatric symptoms (monoamine reuptake inhibitors carry this class risk)

Concurrent serotonergic agents / MAOIs — serotonin-syndrome risk.

Cardiovascular disease / uncontrolled hypertension — caution given BP/HR effects.

Psychiatric history — monoamine modulation can affect mood; caution.

CYP3A4 interactions — long half-life amplifies exposure shifts.

Pregnancy/lactation — no data; avoid.

Regulatory (sport): ⚠️ WADA-banned in-competition — tesofensine is named in the WADA 2026 Prohibited List under S6 (Stimulants) (verified against the archived 2026 list, and corroborated by a 2026 anti-doping publication).[⁴] S6 substances are prohibited in-competition only. Investigational, not FDA-approved, not DEA-scheduled; not approved in Mexico despite claims circulating on vendor sites.

Small molecule

A low-molecular-weight chemical compound, distinct from peptides and proteins.

Oral

Taken by mouth, rather than injected.

Half-life

Roughly how long the body takes to clear half of a dose. A long half-life is why some compounds can be taken only once a week.

WADA Prohibited List

The list of substances banned in regulated sport by the World Anti-Doping Agency.

Investigational

Still being studied and not yet approved by regulators for general use.

1. Astrup A, Madsbad S, Breum L, Jensen TJ, Kroustrup JP, Larsen TM. (2008). Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial (TIPO-1). Lancet, 372(9653):1906–1913.(PMID 18950853 · NCT00394667)
2. Doggrell SA. (2009). Tesofensine — a novel potent weight loss medicine (evaluation of Astrup et al. Lancet 2008). Expert Opin Investig Drugs, 18(7):1043–1046.(PMID 19548858)
3. Lehr T, Staab A, Tillmann C, Trommeshauser D, Raschig A, Schaefer HG, et al. (2007). Population pharmacokinetic modelling of NS2330 (tesofensine) and its major metabolite in patients with Alzheimer's disease. Br J Clin Pharmacol, 64(1):36–48.(PMID 17324246)
4. Krug O, Thomas A, Thevis M. (2026). Investigations Into the Metabolism and Elimination of Tesofensine in Human Urine. Drug Testing and Analysis (published 2026-06-19).(PMID 42320973)
5. Li Y, et al. (2025). Structural basis for pharmacotherapeutic action of triple reuptake inhibitors. Nature Communications, 17(1):61 (2025-12-14).(PMID 41392177)

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