Tesofensine — Triple Monoamine Reuptake Inhibitor (Dopamine/Norepinephrine/Serotonin)

Tesofensine is a potent small-molecule inhibitor of the dopamine, norepinephrine and serotonin transporters (DAT, NET, SERT). Originally developed for neurological disorders, it demonstrated significant weight-loss and metabolic effects in obese human and animal studies.

Identifiers

CAS No.: 195875-84-4
PubChem CID: 11370864
Mechanism class: Triple monoamine reuptake inhibitor (TMI) — DAT, NET, SERT
Approx half-life: ~220 hours (≈9 days) reported in humans; main metabolite ~374 hours.

Mechanism (Plain English)

By blocking the reuptake of dopamine, norepinephrine and serotonin, Tesofensine increases levels of these neurotransmitters in the brain.
This enhanced signaling affects appetite centres (especially in the hypothalamus), leading to reduced food intake (hypophagia) and increased satiety. It also appears to modulate energy-expenditure pathways (via norepinephrine) and feeding-centres (via lateral hypothalamic GABAergic neuron suppression).

Why Researchers Use It

To study central appetite/hunger regulation mechanisms via monoaminergic pathways.
To explore metabolic adaptation after weight loss and energy-balance regulation.
As a comparative tool versus other appetite-suppression or weight-loss agents (e.g., GLP-1 agonists, stimulant analogues).

Key Study Themes — What’s Tested, What Changed, Why It Matters

Diet-Induced Obese Rats: Hypophagia & Weight Loss

What was tested: Rats fed high-fat diet given Tesofensine (0.5-3.0 mg/kg, s.c. for 16 days) and food intake, weight change measured.
What changed: Marked decline in food intake (ED₅₀ ~1.3 mg/kg), significant weight loss vs vehicle.
Why it matters: Demonstrates mechanism of reduced intake + neural-circuit involvement in feeding.

Human Obesity Trial (Phase II) – Body-Weight Loss

What was tested: Obese participants given Tesofensine (0.25 mg, 0.5 mg or 1 mg daily) + diet/exercise for 6 months.
What changed: Average weight loss ~6.7 kg (0.25 mg), ~11.3 kg (0.5 mg), ~12.8 kg (1 mg) over 6 months; placebo ~2.2 kg.
Why it matters: Shows potent appetite/weight outcome compared to older agents—valuable translational data.

Potential Research Applications

Appetite & Hunger Regulation

Hypothalamic circuits, feeding behaviour, GABAergic inhibition in the lateral hypothalamus.

Obesity / Metabolic Adaptation Models

Energy-balance adaptation, post-weight-loss rebound, diet-resistance models.

Monoaminergic Neuropharmacology

DAT/NET/SERT occupancy studies; compare with stimulant / antidepressant models.

Synergistic / Comparator Agents

GLP-1 Agonists

Why compare/partner: Alternative central appetite/hormone signalling; useful to compare mode of action (monoamine vs gut-brain).

Peptides: MOTS-c, CJC-1295/Ipamorelin

Why compare: While Tesofensine targets central monoamines and appetite, peptide blends target metabolic/mitochondrial or GH/IGF axes—combined designs may dissect multiple layers of weight/regulation biology.

Design Notes

Include baseline hunger/appetite questionnaires, neurotransmitter marker panels (if possible), diet/exercise control arms.
Track cardiovascular parameters closely—monoamine modulators often increase HR/BP.

Known Concerns (Context)

Cardiovascular effects:
Stimulant-like risks:
Regulatory status:
Monoamine modulation confounds:

Specifications & Handling

Form: Oral small-molecule compound (lot-coded) — confirm salt/chemical form.
Purity: Research-grade specification (HPLC/MS, ≥98%).
Storage: Manufacturer recommended; typically cool, dry conditions; protect from light/moisture.

In use: Dose and vehicle must be clearly documented; in vivo rodent dosing vs human research differs—specify model and route.

Regulatory & Use Notice

Sold for laboratory research use only. Not for human consumption, medical, or veterinary use. No human-use instructions are provided. Buyer is responsible for safe handling, regulatory compliance, and observing local jurisdiction laws.

Tesofensine Research Compound | Monoamine Reuptake Inhibitor | Appetite Control & Weight-Loss Mechanism Studies

Keywords: Tesofensine, NS2330, triple monoamine reuptake inhibitor, feeding regulation, appetite suppressant research, weight loss pharmacology, DAT NET SERT, Base Peptides.