PMID-24239329 – Tesofensine Dopamine Transporter Occupancy PET
Appel L, Bergstrom M, Buus Lassen J, Langstrom B. Tesofensine, a novel triple monoamine re-uptake inhibitor with anti-obesity effects: dopamine transporter occupancy as measured by PET. Eur Neuropsychopharmacol. 2014;24(2):251-261.
Quick Reference
| Property | Value |
|---|---|
| PMID | 24239329 |
| DOI | 10.1016/j.euroneuro.2013.10.007 |
| Year | 2014 |
| Journal | European Neuropsychopharmacology |
| Study Type | Observational |
| Evidence Level | III |
| Sample | Healthy volunteers (PET imaging study) |
| Peptide(s) Studied | Tesofensine |
Key Findings
- PET imaging confirmed tesofensine occupies dopamine transporters (DAT) in the human brain in vivo
- DAT occupancy at therapeutic doses (0.5 mg) was approximately 30-40%
- This occupancy level is below the threshold associated with abuse potential (~50-60% DAT occupancy)
- Norepinephrine transporter (NET) and serotonin transporter (SERT) occupancy also confirmed
- The triple reuptake inhibition profile was validated in vivo using [11C]PE2I as DAT ligand
- Pharmacokinetic-pharmacodynamic modeling supported once-daily dosing
Study Design
PET neuroimaging study using [11C]PE2I as a DAT-selective radioligand. Subjects received tesofensine at clinical doses and underwent serial PET scans to quantify transporter occupancy over time.
Limitations
- Small sample size typical of PET studies
- Only measured DAT occupancy directly; NET and SERT occupancy inferred
- Healthy volunteers may not reflect occupancy in obese populations
Clinical Relevance
Critical pharmacological study confirming the mechanism of action in humans. The relatively modest DAT occupancy (~30-40%) at therapeutic doses suggests lower abuse liability compared to stimulants like amphetamine (>50% DAT occupancy). This supports tesofensine's positioning as a weight loss agent with acceptable CNS safety profile, distinct from classical stimulants.
Related
#research #observational #tesofensine #evidence-level-III