Tesofensine

Tesofensine (NS2330) is a triple monoamine reuptake inhibitor that blocks the reuptake of dopamine, norepinephrine, and serotonin. Originally developed for Parkinson's and Alzheimer's disease, it demonstrated significant weight loss effects in early trials, leading to its development as an anti-obesity agent. Phase 2 and 3 clinical trials have shown weight loss of 10-12% over 24 weeks, making it one of the more effective investigational weight loss compounds. It works primarily by suppressing appetite and increasing energy expenditure through central nervous system mechanisms.

• Significant Weight Reduction
• Appetite Suppression
• Metabolic Improvements

Potent appetite suppression with significant weight loss (9-12% over 24 weeks). Once-daily oral dosing with long half-life (~9 days). May also increase resting energy expenditure. Different mechanism than GLP-1 agonists offers alternative approach.

Tesofensine is a triple monoamine reuptake inhibitor that blocks reuptake of dopamine (IC50: 6.5nM), norepinephrine (IC50: 1.7nM), and serotonin (IC50: 11nM). This increases neurotransmitter levels in the hypothalamus and other brain regions controlling appetite and satiety. Recent research shows it silences GABAergic neurons in the lateral hypothalamus that normally promote feeding behavior.

Peak plasma concentration: 8 hrs. Elimination half-life: 9.2 days. Largely cleared by: ~45.8 days.

Research protocols from published literature — not dosing recommendations.

• SSRIs (Prozac, Zoloft, etc.) — Avoid Combination: High risk of serotonin syndrome due to overlapping serotonergic activity. Both increase serotonin levels which can lead to dangerous accumulation.
• SNRIs (Effexor, Cymbalta, etc.) — Avoid Combination: Risk of serotonin syndrome and excessive norepinephrine stimulation. Combination may cause severe hypertension and cardiac effects.
• MAOIs — Contraindicated: Absolutely contraindicated. Combination can cause life-threatening serotonin syndrome, hypertensive crisis, and death.
• Stimulants (Adderall, Ritalin) — Avoid Combination: Overlapping dopaminergic and noradrenergic effects may cause severe cardiovascular stress, hypertension, and increased abuse potential.
• Bupropion (Wellbutrin) — Avoid Combination: Both affect dopamine and norepinephrine reuptake. Combination increases risk of seizures, hypertension, and cardiac effects.
• Semaglutide/Tirzepatide — Insufficient Data: No clinical data on combination. Different mechanisms (GLP-1 vs monoamine) but combined use is not recommended without medical supervision.
• Beta-Blockers (Metoprolol) — Potentially Beneficial: Metoprolol may counteract tesofensine-induced heart rate and blood pressure increases while preserving appetite suppression. Studied in preclinical models.
• Caffeine — Use Caution: May enhance stimulant-like effects and cardiovascular stress. Consider reducing caffeine intake while using tesofensine.

Week 1-2: Noticeable appetite reduction, possible dry mouth and mild insomnia. Week 2-4: Initial weight loss begins (1-2kg typical). Month 1-3: Significant weight loss accumulates (5-8% body weight). Month 3-6: Continued weight loss reaching 10-12% in responders. Long half-life (~9 days) means steady levels without peaks/troughs. Effects persist for weeks after discontinuation due to long half-life.

NOT FDA approved - investigational compound only. May increase heart rate by 5-8 bpm (dose-dependent). Can modestly increase blood pressure (1-3 mmHg typical). Contraindicated with MAOIs, SSRIs, SNRIs, and stimulants. Not recommended for those with cardiovascular disease or uncontrolled hypertension. May cause insomnia - take in the morning only. Psychiatric effects possible - avoid with depression/anxiety history. Long half-life means side effects persist if they occur. Regular cardiovascular monitoring recommended.

NOT FDA approved - investigational compound only. May increase heart rate by 5-8 bpm (dose-dependent). Can modestly increase blood pressure (1-3 mmHg typical). Contraindicated with MAOIs, SSRIs, SNRIs, and stimulants. Not recommended for those with cardiovascular disease or uncontrolled hypertension. May cause insomnia - take in the morning only. Psychiatric effects possible - avoid with depression/anxiety history. Long half-life means side effects persist if they occur. Regular cardiovascular monitoring recommended.

Tesofensine should be stored at Room temperature, protect from moisture.