What Is Eutropoflavin (4′-DMA-7,8-DHF)?
Eutropoflavin, also known as 4′-dimethylamino-7,8-dihydroxyflavone, is a synthetic derivative of 7,8-Dihydroxyflavone (7,8-DHF), more commonly referred to as Tropoflavin. It’s gaining attention in the nootropics and neuroscience communities for its ability to mimic brain-derived neurotrophic factor (BDNF) by activating TrkB receptors—the primary receptors involved in synaptic plasticity, memory formation, and neuronal survival.
What makes Eutropoflavin stand out is its enhanced potency and bioavailability compared to Tropoflavin. Research indicates it binds more strongly to TrkB and exerts stronger neurogenic and antidepressant-like effects in animal models (Liu et al., 2010; Liu et al., 2013).
Mechanism of Action
Eutropoflavin acts as a selective TrkB receptor agonist, simulating the action of BDNF. Once bound, it activates several intracellular pathways:
- PI3K/Akt – Promotes cell survival
- MAPK/ERK – Enhances synaptic strength and memory
- PLCγ – Involved in long-term potentiation
Unlike BDNF, which cannot cross the blood-brain barrier, Eutropoflavin is orally bioavailable and readily reaches the brain (Liu et al., 2013). These properties make it a promising candidate for therapeutic use and cognitive enhancement.
Reported Benefits
Cognitive Function and Memory
Users frequently report improved mental clarity, memory recall, and verbal fluency. These claims are supported by preclinical research showing that Tropoflavin—and by extension Eutropoflavin—enhances hippocampal neurogenesis and synaptic plasticity (Yang & Zhu, 2022).
Antidepressant Activity
Eutropoflavin has demonstrated robust antidepressant-like effects in rodents. In both the forced swim test and tail suspension test, it significantly reduced immobility time, a widely accepted indicator of antidepressant potential (Liu et al., 2010; Liu et al., 2013).
Blocking TrkB signaling eliminated these effects, confirming that the antidepressant response is dependent on TrkB pathway activation.
Neuroprotection
Studies show that 7,8-DHF protects dopaminergic neurons from rotenone-induced toxicity—a model of Parkinson’s disease—by reducing oxidative stress and promoting neuron survival (Nie et al., 2019). Given its stronger receptor binding, Eutropoflavin may offer even greater neuroprotective potential.
Side Effects and Safety
Sleep Disruption
A known side effect of Eutropoflavin (and Tropoflavin) is reduced sleep, particularly when taken later in the day. Animal studies confirm a suppression of non-REM sleep and decreased levels of orexin A, a neuropeptide that promotes wakefulness (Feng et al., 2015).
Tolerance and Long-Term Use
Some users report a plateau in benefits with continued use, though no formal studies have examined tolerance or receptor desensitization. Human safety data is limited to anecdotal use, so long-term effects remain unknown.
Dosage and Pharmacokinetics
In rodent studies, effective doses ranged from 5–10 mg/kg orally. Human users typically report doses between 5–20 mg, although no clinical guidelines exist.
Key pharmacokinetic features (Liu et al., 2013):
- Orally bioavailable
- Crosses the blood-brain barrier
- Tmax ~10 minutes
- Plasma half-life ~2 hours
These traits support its use in short, targeted sessions rather than chronic daily dosing.
Comparison: Eutropoflavin vs. Tropoflavin (7,8-DHF)
| Feature | Tropoflavin (7,8-DHF) | Eutropoflavin (4′-DMA-7,8-DHF) |
|---|---|---|
| TrkB Potency | Moderate | High |
| Bioavailability | Variable | Improved |
| Stability | Moderate | Enhanced |
| Antidepressant Effect | Proven | Stronger in preclinical models |
| Neuroprotection | Proven | Potentially greater |
| Human Research | Limited | None |
Conclusion
Eutropoflavin (4’-DMA-7,8-DHF) offers a promising advancement over Tropoflavin, showing enhanced efficacy as a TrkB agonist, stronger antidepressant effects, and neuroprotective potential. Its ability to mimic BDNF while overcoming bioavailability issues makes it especially compelling for both nootropic and therapeutic exploration.
However, despite compelling early data, it’s still unapproved for human medical use, and long-term safety data is nonexistent. If used, it should be approached cautiously—low doses, infrequent use, and daytime administration are advised based on current evidence.
References
- Liu X, Chan CB, Jang SW, et al. A synthetic 7,8-dihydroxyflavone derivative promotes neurogenesis and exhibits potent antidepressant effect. J Med Chem. 2010;53(23):8274-8286. doi:10.1021/jm101206p. PMID: 21073191; PMCID: PMC3150605.
- Liu X, Qi Q, Xiao G, et al. O-methylated metabolite of 7,8-dihydroxyflavone activates TrkB receptor and displays antidepressant activity. Pharmacology. 2013;91(3-4):185-200. doi:10.1159/000346920. PMID: 23445871; PMCID: PMC4793717.
- Yang S, Zhu G. 7,8-Dihydroxyflavone and Neuropsychiatric Disorders: A Translational Perspective from the Mechanism to Drug Development. Curr Neuropharmacol. 2022;20(8):1479-1497. doi:10.2174/1570159X19666210915122820. PMID: 34525922; PMCID: PMC9881092.
- Nie S, Ma K, Sun M, et al. 7,8-Dihydroxyflavone Protects Nigrostriatal Dopaminergic Neurons from Rotenone-Induced Neurotoxicity in Rodents. Parkinsons Dis. 2019;2019:9193534. doi:10.1155/2019/9193534. PMID: 30944722; PMCID: PMC6421741.
- Feng P, Akladious AA, Hu Y, et al. 7,8-Dihydroxyflavone reduces sleep during dark phase and suppresses orexin A but not orexin B in mice. J Psychiatr Res. 2015;69:110-119. doi:10.1016/j.jpsychires.2015.08.002. PMID: 26343602.
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