MEDICAL DISCLAIMER: Educational research guidelines only. Lyophilized peptides are investigational chemical compounds and are NOT approved for human consumption, diagnosis, or therapy. Consult a licensed physician before any research application.
Tesofensine Dosage Chart, Schedule & Reconstitution Protocol
Quickstart Highlights
Tesofensine (NS2330) is an orally active, small-molecule triple monoamine reuptake inhibitor (a phenyltropane) that blocks reuptake of noradrenaline, dopamine and serotonin to suppress appetite and modestly raise energy expenditure (PMID 18950853, PMID 20479765). It was developed by NeuroSearch, first tested without success in Parkinson's and Alzheimer's disease, then repurposed for obesity. In the Phase 2 TIPO-1 trial, 0.5 mg once daily produced about 9-11 kg of weight loss over 24 weeks, roughly double the era's approved drugs, with 0.25-1.0 mg the studied range and 0.5 mg the best efficacy-tolerability balance. It has an unusually long ~9-day half-life plus a long-lived active metabolite (NS2360), so it accumulates over weeks of daily dosing. It is taken orally (>90% bioavailable); the subcutaneous reconstitution scheme here is an educational measurement reference only. Tesofensine is not FDA- or EMA-approved and is sold for research use only.
Reconstitute: Add 2 mL bacteriostatic water → 2.5 mg/mL concentration.
Typical dose: 0.5 mg (500 mcg) once daily orally (studied range 0.25-1.0 mg)
Easy measuring: At 2.5 mg/mL, 1 unit = 0.01 mL = 0.0250 mg (25 mcg) on a U-100 insulin syringe.
Storage: Lyophilized powder stored frozen at −20 °C; reconstituted solution refrigerated at 2-8 °C and used within ~4 weeks. Commercial oral tablets/capsules stored at room temperature, protected from light and moisture.
Half-life: Parent ~9 days (≈220-234 h); active metabolite NS2360 (M1) ~16 days. Levels accumulate over several weeks of daily dosing, supporting once-daily oral use.
Route: Oral once daily (0.25-1.0 mg tablets/capsules), >90% bioavailable; modeled here as a subcutaneous reconstitution reference for measurement only.
Status: Not FDA- or EMA-approved; investigational/research use only (failed Parkinson's/Alzheimer's, Phase 2/early Phase 3 for obesity). Educational content, not medical advice.
About Tesofensine
Tesofensine (NS2330) is a triple monoamine (serotonin-noradrenaline-dopamine) reuptake inhibitor investigated as an anti-obesity agent. Clinically it is taken ORALLY as a once-daily capsule or tablet; the subcutaneous vial-and-bacteriostatic-water figures below are an educational reconstitution reference only, mirroring how this site presents oral compounds, and are not the real-world route [1][7].\n\nThe most studied Tesofensine dosage is 0.5 mg once daily, the dose that gave the best balance of weight loss and tolerability in the Phase 2 TIPO-1 trial. Protocols typically begin at 0.25 mg/day for one to two weeks before stepping up, and 1.0 mg/day was the highest dose tested but added side effects without much extra weight loss [1]. Because tesofensine has a very long half-life of roughly 9 days, blood levels keep climbing for several weeks after a fixed daily dose before reaching steady state, and they decline slowly after stopping [4][5].\n\nThis guide models a 5 mg vial reconstituted with 2 mL of bacteriostatic water (2.5 mg/mL, 25 mcg per insulin-syringe unit) so the small doses land on clean U-100 marks: 0.25 mg = 10 units, 0.5 mg = 20 units, and 1.0 mg = 40 units.\n\nFrequency: Once daily. Tesofensine is not FDA- or EMA-approved and is presented here for educational purposes only.
Quick Protocol Navigation
Reconstitution Instruction & Mixing Step-by-Step
Lyophilized powder must be reconstituted carefully. Agitating peptide chains can shear disulfide bonds and render the peptide biologically inert.
Draw 2 mL of bacteriostatic water into a sterile syringe (this yields a 2.5 mg/mL solution from a 5 mg vial — 25 mcg per insulin-syringe unit).
Inject the water slowly down the inner wall of the 5 mg Tesofensine vial; do not aim the stream directly at the powder, and avoid vigorous shaking.
Gently swirl or roll the vial until the solution is completely clear; the result is a 2.5 mg/mL concentration (25 mcg per U-100 unit).
Store refrigerated at 2-8 °C and draw the units for your step: 0.25 mg ≈ 10 units, 0.5 mg ≈ 20 units, 1.0 mg ≈ 40 units.
Educational note: Tesofensine is clinically taken ORALLY once daily — these subcutaneous reconstitution figures are a measurement reference only; for the educational subcutaneous model, swab the site, inject slowly, and rotate sites.
Interactive Tesofensine Syringe Calculator
Currently visualizing the 5 mg vial reconstituted with 2 mL bacteriostatic water. Adjust the target dose to dynamically render syringe units.
Reconstitution Calculation: 5mg dry powder in 2mL water yields 2.50 mg/mL. To evaluate a 250mcg dose, pull to 10.0 units (10 syringe ticks).
U-100 Syringe Representation
Educational reference visual. Assumes standard U-100 insulin syringe where 1.0 mL volume = 100 units.
Titration & Dose Escalation Schedules
| Phase | Dose per injection | Units (per injection) |
|---|---|---|
| Weeks 1-2 — titration start (0.25 mg) | 250 mcg | 10 units (0.10 mL) |
| Week 3+ — trial-optimal maintenance (0.5 mg) | 500 mcg | 20 units (0.20 mL) |
| Highest dose tested — more side effects (1.0 mg) | 1000 mcg (1 mg) | 40 units (0.40 mL) |
Administration guidelines: Refer to guidelines | 2 mL Reconstitution
Research Supplies Quantity Planner
Scientific mathematical planning of syringes, bacteriostatic water and dry vials needed for extended research blocks using the 5 mg vial.
Peptide Vials (Tesofensine, 5 mg each):
- check8 weeks at 0.5 mg/day ≈ 6 vials (28 mg total)
- check12 weeks at 0.5 mg/day ≈ 9 vials (42 mg total)
- check16 weeks at 0.5 mg/day ≈ 12 vials (56 mg total)
- checkAt 0.25 mg/day usage roughly halves; at 1.0 mg/day it doubles
Insulin Syringes (U-100):
- checkOnce-daily dosing: 7 syringes per week
- check8 weeks ≈ 56 syringes; 12 weeks ≈ 84 syringes; 16 weeks ≈ 112 syringes
- check0.3 mL (30-unit) syringes suffice for 0.25-0.5 mg; the largest 1.0 mg dose is 40 units
Bacteriostatic Water (30 mL bottles): Use 2 mL per 5 mg vial for reconstitution.
- check8 weeks (0.5 mg/day, ~6 vials) ≈ 12 mL ≈ 1 bottle
- check12 weeks (~9 vials) ≈ 18 mL ≈ 1 bottle
- check16 weeks (~12 vials) ≈ 24 mL ≈ 1 bottle
Alcohol Swabs:
- check1-2 swabs per dose (vial top + injection site)
- check8 weeks ≈ 60-120 swabs; 12 weeks ≈ 90-170 swabs
- check16 weeks ≈ 120-230 swabs; keep extras for re-swabbing multi-use vials
Mechanism of Action (MOA)
Tesofensine is not a peptide; it is a small-molecule phenyltropane derivative (chemical formula C17H23Cl2NO, CAS 195875-84-4) that inhibits the presynaptic transporters for all three major monoamine neurotransmitters: the noradrenaline transporter (NET), the serotonin transporter (SERT) and the dopamine transporter (DAT). Reported in-vitro potencies are roughly IC50 1.7 nM at NET, 11 nM at SERT and 65 nM at DAT, so the compound is most strongly noradrenergic and serotonergic with weaker dopaminergic activity [7]. By blocking reuptake it raises synaptic concentrations of these monoamines, amplifying signaling in hypothalamic and mesolimbic circuits that govern hunger, satiety and reward [3].\n\nPreclinical work in diet-induced obese rats showed that tesofensine's appetite suppression is mediated indirectly: the hypophagic effect was almost completely reversed by the α1-adrenoceptor antagonist prazosin and partly by the dopamine D1 antagonist SCH23390, implicating downstream α1-adrenergic and D1-dopaminergic pathways rather than direct receptor agonism [3]. In humans, a controlled metabolic-chamber study found that tesofensine both reduced appetite/energy intake and increased 24-hour energy expenditure and fat oxidation, a dual mechanism that helps explain its larger weight-loss effect compared with appetite suppressants acting on intake alone [2].\n\nPharmacokinetically, tesofensine is suited to once-daily oral dosing but behaves very differently from short-acting peptides. Absolute oral bioavailability exceeds 90%, plasma protein binding is about 91%, and the volume of distribution is large (well above total body water), indicating extensive tissue distribution [4]. Total body clearance is low (about 30-40 mL/min), and the kidney accounts for only ~15-20% of elimination; metabolism is primarily hepatic. The defining feature is an unusually long terminal half-life — roughly 9 days (around 220-234 hours) — together with a single major active metabolite, the N-desmethyl compound NS2360 (M1), whose half-life is even longer (near 16 days) and which reaches roughly a third of parent exposure at steady state [4][5]. Practically, this means a fixed daily dose accumulates for several weeks before steady state, and concentrations decline slowly after stopping.\n\nThe real-world route is oral once-daily tablets/capsules; the subcutaneous reconstitution scheme on this page is an educational measurement convention used across this site, not a clinically validated delivery method. Tesofensine was first studied (without success) for Parkinson's and Alzheimer's disease before being repurposed for obesity; it is not approved by the FDA, EMA or any major regulator and remains investigational [1][7].
Clinical Trial Efficacy Highlights
- starIn the Phase 2b TIPO-1 trial (Astrup et al., Lancet 2008), 203 obese adults on a calorie-restricted diet received tesofensine 0.25, 0.5 or 1.0 mg or placebo once daily for 24 weeks; mean weight loss beyond diet and placebo was approximately 4.5%, 9.2% and 10.6% respectively (about 6.7, 11.3 and 12.8 kg total versus ~2.2 kg on placebo), roughly double the effect of obesity drugs available at the time [1].
- starA randomized metabolic-chamber study in overweight and moderately obese men (Sjödin et al., Int J Obes 2010) showed tesofensine suppressed appetite and energy intake while also increasing 24-hour energy expenditure and fat oxidation, indicating a dual intake-plus-expenditure mechanism rather than appetite suppression alone [2].
- starMechanistic work in diet-induced obese rats (Axel et al., Neuropsychopharmacology 2010) found tesofensine produced dose-dependent hypophagia (ED50 ~1.3 mg/kg) that was almost fully blocked by the α1-adrenoceptor antagonist prazosin and partly by the D1 antagonist SCH23390, mapping its appetite effect to downstream noradrenergic and dopaminergic pathways [3].
- starPopulation pharmacokinetic modelling in Alzheimer's patients (Lehr et al., Br J Clin Pharmacol 2007) estimated absolute oral bioavailability >90%, a parent half-life of about 234 hours (~9-10 days), low oral clearance and extensive tissue distribution, establishing the long-acting profile that drives accumulation over weeks of daily dosing [4].
- starA pharmacokinetic-pharmacodynamic modelling analysis of the active metabolite M1/NS2360 (Lehr et al., Br J Pharmacol 2008) characterized its even longer half-life (~16 days) and ~31-34% of parent exposure at steady state, showing the metabolite contributes a small but measurable share of overall pharmacological activity [5].
- starIn hypothalamic obesity — a notoriously treatment-resistant condition — the Phase 2 Tesomet trial (Huynh et al., Eur J Endocrinol 2022) combined 0.5 mg tesofensine with 50 mg metoprolol; over 24 weeks Tesomet produced a placebo-subtracted weight reduction of about 6.3%, with 8 of 13 treated patients losing ≥5% and no significant rise in heart rate or blood pressure versus placebo (metoprolol was added specifically to blunt cardiovascular effects) [6].
- starIn the open-label TIPO-4 extension, patients who continued 0.5 mg tesofensine achieved further weight loss, with reported total mean reductions of roughly 13-14 kg over about 48 weeks, suggesting durable efficacy with continued dosing, although no completed Phase 3 obesity trial has yet confirmed long-term safety and efficacy [7].
Side Effects & Tolerability Profile
Clinical subjects transiently report mild side effects. Slowly escalating the titration dose represents the single most effective intervention to limit side effects.
- warningThe most common adverse effects in obesity trials were dry mouth, headache, nausea, insomnia, diarrhea and constipation; dry mouth and insomnia were clearly dose-dependent and more frequent at 1.0 mg/day [1][7].
- warningTesofensine raises blood pressure and heart rate through its noradrenergic activity: at therapeutic 0.25-0.5 mg doses increases were modest (about 1-3 mmHg and up to ~8 bpm), but cardiovascular monitoring is warranted and higher doses amplify these effects [1].
- warningBecause it boosts dopamine and serotonin signaling, tesofensine can cause mood and sleep changes; the Lancet trial flagged a signal for increased psychiatric/mood-related events, and it should not be combined with MAO inhibitors or other serotonergic or stimulant drugs [1].
- warningThe trial dropout rate for adverse events was higher on tesofensine (~13%) than placebo (~6%), driven largely by the 1.0 mg dose, which is why 0.5 mg is considered the optimal efficacy-tolerability balance [1][7].
- warningThe very long half-life (~9 days for parent, ~16 days for the active metabolite NS2360) means effects and side effects persist for weeks after stopping and that levels accumulate during daily dosing — important for managing drug interactions, overdose and washout [4][5].
- warningContraindications and cautions follow from the mechanism: uncontrolled hypertension, cardiovascular disease, arrhythmia, history of psychiatric illness or substance use, and concurrent stimulants, sympathomimetics or serotonergic agents; safety in pregnancy, lactation and pediatric use has not been established.
- warningMetabolism is largely hepatic; drugs affecting hepatic enzymes or other monoaminergic agents may alter exposure or risk, and combining tesofensine with other appetite suppressants is not supported by controlled data.
- warningRegulatory/research status: tesofensine is NOT approved by the FDA, EMA or any major regulator for obesity or any other indication; it remains investigational and is sold only for research. Long-term human safety is not established, and this page is educational, not medical advice [1][6][7].
Subcutaneous Injection Technique
Most research peptides require subcutaneous injection into fatty tissue. Never inject directly into a blood vessel or deep muscle tissue unless clinically detailed.
1. Site Selection
Common locations include the abdomen (2 inches from navel), outer upper arms, or thighs.
2. Sanitization
Thoroughly clean the selected site, stopper and vial top using 70% isopropyl alcohol prep swabs.
3. Angle & Push
Pinch the skin and insert the needle at a 45 to 90-degree angle. Depress plunger smoothly.
4. Site Rotation
Rotate injection sites continuously to avoid lipodystrophy or tissue scarring.
Frequently Asked Questions
What is the typical Tesofensine dosage?expand_more
In the Phase 2 TIPO-1 trial the studied oral range was 0.25 to 1.0 mg once daily, and 0.5 mg/day gave the best balance of weight loss (about 9-11 kg over 24 weeks) and tolerability, so 0.5 mg once daily is generally regarded as the trial-optimal Tesofensine dosage. Many protocols start at 0.25 mg/day for one to two weeks before stepping up. The 1.0 mg dose added little extra weight loss while increasing dry mouth, insomnia, blood pressure and heart rate. It is taken orally; the subcutaneous figures on this page are an educational measurement reference only.
Is Tesofensine FDA approved?expand_more
No. Tesofensine is not approved by the FDA or EMA for obesity or any other indication. It was originally developed by NeuroSearch for Parkinson's and Alzheimer's disease (where it failed), then repurposed for obesity, reaching Phase 2 and early Phase 3 development. It is investigational and sold only for research use; this page is educational, not medical advice.
What is the half-life of Tesofensine?expand_more
Tesofensine has an unusually long terminal half-life of about 9 days (roughly 220-234 hours), and its active metabolite NS2360 (M1) persists even longer, near 16 days. Absolute oral bioavailability exceeds 90%. Because of this long half-life, blood levels accumulate for several weeks of once-daily dosing before reaching steady state and then decline slowly after stopping, so a single daily dose is sufficient and a single missed dose has limited short-term impact.
How is Tesofensine reconstituted and dosed?expand_more
Clinically tesofensine is swallowed as a tablet or capsule, so no reconstitution is needed in real-world use. For the educational subcutaneous model on this site, a 5 mg vial is mixed with 2 mL of bacteriostatic water to give 2.5 mg/mL (25 mcg per U-100 unit): draw the water slowly down the vial wall, swirl gently until clear, and refrigerate. At that concentration 0.25 mg measures 10 units, 0.5 mg measures 20 units and 1.0 mg measures 40 units on an insulin syringe.
Can Tesofensine be stacked with other compounds?expand_more
In research, tesofensine has been combined with the beta-blocker metoprolol (the Tesomet combination) specifically to blunt its blood-pressure and heart-rate effects, and that pairing showed weight loss without significant cardiovascular changes in a Phase 2 hypothalamic-obesity trial. However, stacking with other stimulants, sympathomimetics, serotonergic drugs or MAO inhibitors is dangerous and not supported, and there is no validated protocol for combining it with other weight-loss agents. Treat any combination as experimental.
Related Guides & Tools
Step-by-step references for reconstituting, measuring, and storing Tesofensine, plus the universal dosing calculator.
Academic References & Study Citations
Astrup A, Madsbad S, Breum L, Jensen TJ, Kroustrup JP, Larsen TM. 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. 2008;372(9653):1906-1913. View Scientific Paper →
Sjödin A, Gasteyger C, Nielsen AL, et al. The effect of the triple monoamine reuptake inhibitor tesofensine on energy metabolism and appetite in overweight and moderately obese men. Int J Obes (Lond). 2010;34(11):1634-1643. View Scientific Paper →
Axel AM, Mikkelsen JD, Hansen HH. Tesofensine, a novel triple monoamine reuptake inhibitor, induces appetite suppression by indirect stimulation of α1 adrenoceptor and dopamine D1 receptor pathways in the diet-induced obese rat. Neuropsychopharmacology. 2010;35(7):1464-1476. View Scientific Paper →
Lehr T, Staab A, Tillmann C, Trommeshauser D, Raschig A, Schaefer HG, Kloft C. Population pharmacokinetic modelling of NS2330 (tesofensine) and its major metabolite in patients with Alzheimer's disease. Br J Clin Pharmacol. 2007;64(1):36-48. View Scientific Paper →
Lehr T, Staab A, Tillmann C, Nielsen EØ, Trommeshauser D, Schaefer HG, Kloft C. Contribution of the active metabolite M1 to the pharmacological activity of tesofensine in vivo: a pharmacokinetic-pharmacodynamic modelling approach. Br J Pharmacol. 2008;153(1):164-174. View Scientific Paper →
Huynh K, Klose M, Krogsgaard K, et al. Randomized controlled trial of Tesomet (tesofensine 0.5 mg + metoprolol 50 mg) for weight loss in hypothalamic obesity. Eur J Endocrinol. 2022;186(6):687-700. View Scientific Paper →
Tesofensine (NS2330) — overview, development history (NeuroSearch/Saniona), pharmacology, TIPO-1/TIPO-4 trials and regulatory status. Wikipedia. View Scientific Paper →