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Triple monoamine reuptake inhibitor (phenyltropane)
Metabolic / Weight Management

Tesofensine

Triple monoamine reuptake inhibitor examined for CNS approach to appetite signaling.

Mechanism of Action

Compound targeting metabolic efficiency and cellular energy production.

Evidence Chain

Tesofensine

COMPOUND

1 Research Goal

• Weight Management

Evidence Strength

Clinical Trial

23 articles sourced

Knowledge Graph

(24 connections)
CompoundGoalArticleArticleArticle
Compound (Center)
Research Goal
Linked Article

Research Evidence

(23)

Ligandrol (LGD-4033): Evidence-Based Research Review

5 min

Ligandrol (LGD-4033), also known as VK5211, is a potent, non-steroidal selective androgen receptor modulator (SARM) developed for the treatment of conditions characterized by muscle wasting and osteoporosis. As a SARM, it is designed to exert anabolic effects on skeletal muscle and bone while minimi

Clinical Trial

Enobosarm (Ostarine / MK-2866): Evidence-Based Research Review

5 min

**Class:** SARM (Selective Androgen Receptor Modulator)

Clinical Trial

Clomiphene Citrate: Evidence-Based Research Review

6 min

Clomiphene citrate (CC) is a non-steroidal triphenylethylene derivative classified as a Selective Estrogen Receptor Modulator (SERM). Originally developed for the induction of ovulation in women with anovulatory infertility, it has become a cornerstone of reproductive medicine. CC operates as a race

Clinical Trial

Tamoxifen Citrate: Evidence-Based Research Review

6 min

Tamoxifen citrate is a non-steroidal triphenylethylene derivative and the prototypic Selective Estrogen Receptor Modulator (SERM). Originally developed as a contraceptive, it has become a cornerstone in the treatment and prophylaxis of estrogen receptor-positive (ER+) breast cancer. Tamoxifen exhibi

Clinical Trial

Oxandrolone: Evidence-Based Research Review

6 min

Oxandrolone (17β-hydroxy-17α-methyl-2-oxa-5α-androstan-3-one) is a synthetic oral anabolic-androgenic steroid (AAS) derived from dihydrotestosterone (DHT). Characterized by a unique substitution of an oxygen atom for the carbon at the C-2 position in the A-ring, oxandrolone exhibits a high anabolic-

Clinical Trial

Nandrolone Decanoate: Evidence-Based Research Review

6 min

Nandrolone decanoate (ND) is a long-acting injectable ester of the anabolic-androgenic steroid (AAS) nandrolone (19-nortestosterone). Characterized by a high anabolic-to-androgenic ratio, ND has been utilized clinically for decades to treat conditions involving protein catabolism, bone density loss,

Clinical Trial

Testosterone Enanthate: Evidence-Based Research Review

6 min

Testosterone enanthate (TE) is a long-acting esterified formulation of the primary endogenous androgen, testosterone. Since its clinical introduction in the 1950s, it has served as a cornerstone for testosterone replacement therapy (TRT) in male hypogonadism and a reference compound in clinical rese

Clinical Trial

Toremifene Citrate: Evidence-Based Research Review

5 min

Toremifene citrate is a chlorinated triphenylethylene derivative and a second-generation selective estrogen receptor modulator (SERM). Structurally analogous to tamoxifen, toremifene was developed to maintain the therapeutic efficacy of ER-antagonism in breast tissue while potentially improving the

Clinical Trial

Raloxifene: Evidence-Based Research Review

6 min

Raloxifene is a second-generation selective estrogen receptor modulator (SERM) of the benzothiophene class. Developed to address the limitations of first-generation SERMs like tamoxifen, raloxifene exhibits distinct tissue-specific effects: it acts as an estrogen receptor (ER) agonist in bone and li

Clinical Trial

Methenolone Enanthate: Evidence-Based Research Review

6 min

Methenolone enanthate is a long-acting injectable anabolic-androgenic steroid (AAS) derived from dihydrotestosterone (DHT). Characterized by a 1-methyl modification and a 2-oxo group, it exhibits a high anabolic-to-androgenic ratio and is notable for its inability to aromatize into estrogen. Origina

Clinical Trial

Stanozolol: Evidence-Based Research Review

5 min

Stanozolol is a synthetic anabolic-androgenic steroid (AAS) derived from dihydrotestosterone (DHT). Characterized by a high anabolic-to-androgenic ratio, it is clinically distinguished by its pyrazole ring modification and 17α-alkylation. Originally developed for the treatment of hereditary angioede

Clinical Trial

Survodutide (BI 456906): Dual GLP-1/Glucagon Receptor Agonist — Clinical Evidence in Obesity and MASH

6 min

Survodutide is a dual GLP-1 and glucagon receptor agonist in clinical development by Boehringer Ingelheim for obesity and metabolic dysfunction-associated steatohepatitis (MASH). This review summarizes the clinical evidence.

Clinical Trial

CagriSema (Cagrilintide + Semaglutide) Combination Therapy: Clinical Evidence from the REDEFINE Trial Program

6 min

CagriSema combines cagrilintide (a long-acting amylin analogue) with semaglutide (a GLP-1 receptor agonist) for the treatment of obesity. The REDEFINE clinical development program evaluates the additive weight-loss effects of co-administering amylin and incretin pathway agonism.

Clinical Trial

GLP-1 Receptor Agonism in Metabolic Signaling

8 min

Survey of GLP-1, GIP, and glucagon receptor research for metabolic signaling and incretin physiology.

Clinical Trial

Telomerase Activation and Cellular Senescence Pathways

9 min

Survey of telomerase and mitochondrial peptide research in aging and senescence pathways.

Clinical Trial

YK-11: Evidence-Based Research Review

5 min

YK-11 (17α,20E)-17,20-[(1-methoxyethylidene)bis(oxy)]-3-oxo-19-norpregna-4,20-diene-21-carboxylic acid methyl ester is a synthetic compound classified as a Selective Androgen Receptor Modulator (SARM). Unlike traditional non-steroidal SARMs such as Ostarine or Ligandrol, YK-11 possesses a steroidal

Peer-Reviewed

Testolone (RAD-140): Evidence-Based Research Review

5 min

Testolone (RAD-140) is a potent, non-steroidal selective androgen receptor modulator (SARM) originally developed by Radius Health, Inc. It was designed to overcome the limitations of conventional androgen therapy, such as prostate enlargement and virilization, by exhibiting high tissue selectivity.

Preclinical

Cardarine (GW-501516): Evidence-Based Research Review

6 min

Cardarine (GW-501516) is a synthetic peroxisome proliferator-activated receptor delta (PPARδ) agonist originally developed through a collaboration between Ligand Pharmaceuticals and GlaxoSmithKline (GSK) for the treatment of metabolic and cardiovascular diseases. Although frequently categorized as a

Preclinical

Andarine (S-4): Evidence-Based Research Review

5 min

Andarine (also known as S-4 or GTx-007) is an early-generation, nonsteroidal selective androgen receptor modulator (SARM) belonging to the aryl propionamide class. Developed initially for the treatment of conditions such as muscle wasting and osteoporosis, Andarine demonstrates high affinity for the

Preclinical

Drostanolone Propionate: Evidence-Based Research Review

6 min

Drostanolone propionate (2α-methyl-5α-androstan-17β-ol-3-one propionate) is a synthetic anabolic-androgenic steroid (AAS) derived from dihydrotestosterone (DHT). Originally developed for the treatment of advanced breast cancer in postmenopausal women, it is characterized by its inability to aromatiz

Preclinical

Boldenone Undecylenate: Evidence-Based Research Review

6 min

Boldenone undecylenate, a synthetic derivative of testosterone originally developed for veterinary use, is a long-acting injectable anabolic-androgenic steroid (AAS). Characterized by a double bond between the C1 and C2 positions, the compound exhibits a favorable ratio of anabolic to androgenic act

Preclinical

Trenbolone Acetate: Evidence-Based Research Review

6 min

Trenbolone acetate (TBA) is a potent synthetic 19-nortestosterone derivative classified as an anabolic-androgenic steroid (AAS). Originally developed for veterinary applications—specifically to increase muscle mass and feed efficiency in beef cattle—TBA has become a focal point of pharmacological in

Preclinical

Adalank and the Selank Peptide Class: Anxiolytic Peptide Pharmacology and Translational Rationale

6 min

Adalank is a synthetic analog of the anxiolytic peptide Selank incorporating an adamantane moiety. This review outlines the pharmacological rationale and preclinical evidence from the Selank peptide class that informs its development.

Preclinical

Overview

Tesofensine is a triple monoamine reuptake inhibitor (inhibiting the reuptake of serotonin, noradrenaline, and dopamine) developed by NeuroSearch for the treatment of obesity and neurological conditions. While not a peptide, Tesofensine is included in research contexts alongside metabolic peptides due to its novel CNS-based approach to appetite regulation and weight management. It represents a non-incretin approach to metabolic therapy.

Mechanism of Action

Tesofensine inhibits the reuptake of three key neurotransmitters: serotonin (5-HT), noradrenaline (NA), and dopamine (DA). By preventing reuptake, Tesofensine increases the synaptic concentration of these neurotransmitters, producing effects on appetite regulation, energy expenditure, and satiety. The triple monoamine mechanism is distinct from incretin-based therapies, offering an alternative pathway for weight management. The dopaminergic component may also contribute to effects on reward-based eating behavior.

Research Highlights

Clinical trials demonstrated Tesofensine's efficacy in producing weight loss, with Phase II trials showing mean weight loss of 6.7-12.6% over 24 weeks at doses of 0.25-1.0 mg. Research showed significant reductions in appetite and food intake, with improvements in metabolic markers. Studies explored its potential in Parkinson's disease and Alzheimer's disease due to its dopaminergic and noradrenergic activity. Despite promising weight loss results, development for obesity was paused, and the compound has been investigated in niche neurological applications.

Dosage & Administration

In clinical trials, Tesofensine was administered orally at doses of 0.25-1.0 mg once daily. For research use only (RUO).

Safety Profile

Common side effects include dry mouth, insomnia, nausea, constipation, and increased heart rate. The cardiovascular effects (heart rate increase, blood pressure changes) have been a regulatory concern. Psychiatric effects including mood changes have been reported. Long-term safety data is limited. Not approved by the FDA for any indication.

References

Astrup A, et al. Tesofensine for obesity. Lancet. 2008. Sjodin A, et al. Tesofensine Phase II. Int J Obes. 2010. NeuroSearch clinical trial data. All content is for educational and research purposes only.

Synergy & Compatibility

(5)

Computational assessment of bio-regulatory compatibility with compounds sharing research goals. Scores reflect half-life alignment, receptor target overlap, and bioavailability data.

View full comparison matrix

Computational assessment based on available pharmacology data. Does not account for individual variability, dose-dependent effects, or unstudied interactions. For research use only.

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(0)

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