Pharmaceuticals

Tesofensine

Evidence: moderate_human

Mechanism of Action

Tesofensine (NS2330) is a triple monoamine reuptake inhibitor with affinity for dopamine (DAT), serotonin (SERT), and norepinephrine (NET) transporters. It suppresses appetite through indirect stimulation of alpha-1 adrenoceptor and dopamine D1 receptor pathways, reflecting additive effects of increased NE and DA activity. Tesofensine is a dual-action drug with both anorexigenic properties (appetite suppression) and metabolic properties (increased energy expenditure), silencing GABAergic hypothalamic neurons in the lateral hypothalamus.

Dosing Protocol

Standard: Research indicates 0.25-0.5 mg daily via oral administration.

Loading: Research indicates starting at 0.125 mg daily for the first week, titrating up to 0.25-0.5 mg.

Maintenance: Research indicates 0.25 mg daily for maintenance.

Administration: oral

Timing: Morning dosing only. Avoid afternoon/evening dosing due to stimulant properties and potential insomnia.

Duration: 12-24 week cycles. Monitor cardiovascular parameters throughout.

Notes

Tesofensine is technically a small molecule drug, not a peptide, but is included in metabolic optimization protocols. It produced approximately 2x the weight loss of sibutramine in clinical trials. The cardiovascular side effect profile (increased HR and BP) requires careful screening — clients must have baseline cardiovascular assessment including ECG and blood pressure monitoring. Not recommended for clients with any cardiovascular risk factors. Originally developed for Alzheimer's/Parkinson's disease where its weight loss effects were discovered as a side effect.

Stacking

  • AOD-9604
  • 5-Amino-1MQ

Interactions

  • MAO inhibitors [HIGH] — Serotonin syndrome risk — absolute contraindication with MAOIs.
  • SSRIs/SNRIs [HIGH] — Additive serotonergic and noradrenergic effects; serotonin syndrome risk.
  • Stimulants (amphetamines, methylphenidate) [HIGH] — Additive monoamine reuptake inhibition; cardiovascular risk.
  • Antihypertensives [MEDIUM] — Tesofensine may increase blood pressure and heart rate, counteracting antihypertensives.
  • Can stack dangerously with stimulants or serotonergic agents

Contraindications

  • Uncontrolled hypertension
  • History of cardiovascular disease
  • Concurrent MAOI use
  • Glaucoma
  • Hyperthyroidism
  • Pregnancy and breastfeeding
  • History of seizures
  • Anorexia nervosa
  • Cardiovascular disease
  • Uncontrolled anxiety

Side Effects

  • Increased heart rate
  • Elevated blood pressure
  • Dry mouth
  • Insomnia
  • Constipation
  • Nausea
  • Headache
  • Anxiety/restlessness

Key Papers

  • 10.1038/npp.2010.16
  • 10.1038/ijo.2010.87
  • Obesity-drug literature on tesofensine

Source Quality

Compounding pharmacy. Not FDA-approved. Phase III trials completed in some markets. Requires careful cardiovascular monitoring.

Disclaimer: This information is for educational purposes only and is not medical advice. BioAccelera Labs does not diagnose, treat, or prescribe. Consult a licensed healthcare provider before using any compound.

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