MetabolicPhase III

Tesofensine

NS2330

A triple monoamine reuptake inhibitor being developed for obesity. Inhibits serotonin, norepinephrine, and dopamine reuptake to reduce appetite and increase metabolism.

What is Tesofensine?

Tesofensine is a triple monoamine reuptake inhibitor originally developed for Parkinson's and Alzheimer's disease that showed significant weight loss effects. It inhibits reuptake of serotonin, dopamine, and norepinephrine, reducing appetite and increasing energy expenditure.

Note: Not a peptide but a small molecule often grouped with metabolic research compounds.


Development History

  • Originally developed for neurodegenerative diseases
  • Phase 2 trials for Parkinson's and Alzheimer's
  • Efficacy insufficient for CNS indications
  • BUT significant weight loss observed
  • Redirected to obesity development

Mechanism

Triple Reuptake Inhibition

Inhibits reuptake of:

  • Serotonin: Satiety effects
  • Norepinephrine: Energy expenditure
  • Dopamine: Reward/motivation

Together produce:

  • Appetite suppression
  • Increased metabolism
  • Reduced food reward

Clinical Results

Phase 2 obesity trials showed:

  • 10-13% weight loss at 6 months
  • Superior to existing medications at the time
  • Dose-dependent effects

Status

  • Phase 3 trials ongoing
  • Not yet approved
  • Heart rate/BP concerns being monitored
  • Potential future obesity treatment

Summary

Key Points:

  • Classification: Triple reuptake inhibitor
  • Mechanism: 5-HT, NE, DA reuptake
  • Effect: Weight loss
  • Status: Phase 3 development

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